Zona limitans intrathalamica
Encyclopedia
The zona limitans intrathalamica (ZLI) is a lineage-restriction compartment and primary developmental boundary in the vertebrate
forebrain (which is analogous to the human cerebrum) that serves as a signaling center and a restrictive border between the thalamus
(also known as the dorsal thalamus) and the prethalamus
(ventral thalamus). Sonic hedgehog
(shh) signaling from the ZLI is crucial in the development of the diencephalon
, which develops into the thalamus
, the pretectum
, and the anterior tegmental
structures. The ZLI together with the prethalamus and thalamus make up the mid-diencephalic territory (MDT).
s, where the expression of various Hox genes in each compartment confer the differentiation of observable segments in the adult body of Drosophila melanogaster
. Analogous structures were discovered in the developing vertebrate
brain
. Rhombomere
s, which extend down the embryo
from the hindbrain, contain clear boundaries and each express various Hox genes that are necessary for differentiation
of structures within the body. More anterior regions of the brain
were examined in search of other cell lineage restriction boundaries, and multiple potential boundaries continue to be studied (see Developmental Boundaries).
The importance of these compartments as local signaling centers, areas which chemically
influence surrounding tissue
, was elucidated by first observing differential expression
of Hox genes in various compartments and second by observing mutant D. melanogaster
and corresponding phenotypic
(physical) changes.
The ZLI was first discovered in the chick
using explant
and lineage-labeling experiments. In the explant experiments, cells in the region that will become the ZLI, the prethalamus
, and the thalamus
in the chick were removed and placed into separate cultures
; the cells continued to grow and retained their identity (the ZLI began transcribing
, whereas the prethalamus
and thalamus
did not). Necessity of the ZLI and its corresponding ' expression were evidenced by lack of thalamic and prethalamic genetic markers in culture (see Signaling). These experiments confirmed the ZLI as a signaling center. In lineage-labeling experiments, cells were genetically marked, so that each time a labeled cell replicated, its progeny
were marked as well. Cells that were marked in the developing ZLI and their progeny remained restricted to the zone. These experiments demonstrated the ZLI as a cell-lineage restriction boundary.
Not only a boundary, the ZLI is also a compartment with separate cell lineage restriction boundaries both anterior and posterior of a section of shh
expression. The importance of the ZLI was once more confirmed by ectopic expression
of shh
in other regions of the forebrain, known as the prosencephalon
during development (both the telencephalon
and diencephalon
), inducing a ZLI-like region that induces thalamic fate.
in both vertebrate
s and invertebrate
s, cell lineage restriction boundaries and signaling centers are formed in order to ensure proper differentiation
of the body. Chemical signals
, like shh
from the ZLI, are often released from these boundaries and compartments in a concentration
gradient (the chemicals are in much higher concentrations closer to the source) and confer identity to flanking regions. Other genes differentially expressed
in these flanking regions aid in ensuring proper differentiation (see Signaling).
Many developmental boundaries have been studied: within the forebrain alone, the confirmed cell lineage restriction boundaries are the pallial-subpallial boundary (PSB) dividing the dorsal and ventral telencephalon, the diencephalon-midbrain boundary (DMB) posterior to the ZLI, and the ZLI. The ZLI, like each rhombomere
, serves as an independent compartment that confers the identity of diencephalon
in anterior and posterior regions. Other developmental boundaries serve as cell-lineage restriction boundaries but not signaling centers, while others are signaling centers to and from which cells can migrate. Despite discoveries of cell lineage restriction boundaries and compartments in the brain, many of the regions studied have been disproven as segmental boundaries. These areas have potential as signaling centers, which have influence over the development of neighboring tissues.
These boundaries have great influence over other regions of the brain: the placement of the ZLI not only affects the size of adjacent regions but also the size of the telencephalon
. A posterior shift in the ZLI allows more cells to be allocated to the telencephalon
. The same is true for other developmental boundaries in the brain and throughout the body: shifts in boundaries responsible for allocating a certain amount of tissue to a certain function result in drastic changes in the adult structure. These boundaries are of crucial importance for proper differentiation.
, the embryo
is completely undifferentiated
and requires many different cues to initiate proper differentiation
of the body. The top (roof plate, on the dorsal side of the embryo) and bottom (floor plate, on the ventral side) play a crucial role in these first steps: each acts through global signaling
(signaling throughout the entire embryo) for dorsoventral
neural patterning. After completion of the development
of the dorsoventral
axis, more local signaling occurs in the developing brain: developmental boundaries such as the midbrain-hindbrain boundary (MHB), rhombomere
s, and the ZLI aid in anteroposterior
organization.
patterning, shh
is expressed along the basal plate
(the bottom) of the embryo
, which functions in “ventralization
of the neural tube
, promotion of growth and proliferation
, and formation of the hypothalamus
”. As the embryo
continues to develop
, shh
expression characteristic of the ZLI extends dorsally
to form a wedge that eventually narrows to a strip at approximately 22 somite
s (the number of developed rhombomere
s) or less than one day in zebrafish. Although shh
expression extends dorsally
from the basal plate
, the ZLI is capable of forming even without the basal plate
or mesoderm
al tissue. Shh
cooperates with dlx2
and fezl anteriorly
and irx3 and dbx1a posteriorly (genes expressed vary among different organisms), which are gene
s that are expressed in the prethalamus
and thalamus
, respectively.
The ZLI is also characterized by a lack of lunatic fringe
(lfng), which is observable even before shh
expression is observed in the forming ZLI. This indicates that cells are fated for ZLI formation before induction by shh
(n.b. shh
signals from the ZLI and is characteristic of the compartment during and after formation). Lfng
is expressed very early (soon after gastrulation
) in the region that will become the ZLI, but shortly thereafter expression recedes through migration of lfng
-expressing cells to form the lfng
-free wedge characteristic of the developing ZLI. Shh
expression does not extend dorsally
until a few hours later.
s further complicate elucidation of the pathways
, specifically between chicks/ mammal
ian models and zebrafish.
Wnt
(the family wingless) genes are crucial for the development of the ZLI both directly and indirectly in all animal systems. Along with the role of Wnt
genes in patterning the anteroposterior
axis through gradient polarization, Wnt8b
is expressed within the ZLI itself and may help guide dorsal
movement of shh
expression. The Wnt
polarization gradient has been linked to induction of ZLI-patterning genes irx3 and six3
, which border the ZLI posteriorly
and anteriorly
, respectively. However, these gene
s have been shown to be non-essential for ZLI formation in zebrafish and have been reevaluated in other models.
Specification of the ZLI may also involve the ventral tissues
of the embryo
: the prechordal
and epichordal plates, or neuroepithelial tissue (see figure). Interactions between these tissues may be responsible for the recession of expression of lfng
which allows dorsal
movement shh
expression. The specific prechrodal and epichordal plates, characterized by expression of six3
and irx3, respectively, may influence positioning of the ZLI more so than the genes themselves. The prechrodal plate ventrally borders the telencephalon
, with the epichrodal plate posterior
to it.
Studies of the formation of the ZLI performed in zebrafish have revealed the significance of otx2 and irx1 in ZLI positioning. Otx2 expression characterizes the developing optic tectum
, which is responsible for sight processing. Expression extends anteriorly
and ends sharply at the ZLI, with high expression
along the line where shh
is expressed. Before the ZLI is formed, otx2 is expressed ubiquitously throughout the forebrain, and begins to recede to the position of the putative ZLI. Experiments where otx2 expression was repressed showed no dorsal
movement of shh
expression and no ZLI formation. Irx1, which is analogous to irx3 in birds and mammals, is expressed posterior to the ZLI. Studies have suggested that while otx2 positively restricts the ZLI anteriorly (shh
cannot be expressed where otx2 is not), irx1 negatively restricts the ZLI posteriorly. Other genes crucial for differentiation in the brain, including Fgf genes responsible for patterning of the midbrain-hindbrain boundary (MHB), have been implicated in positioning of the ZLI.
Studies on the role of shh
signaling in the ZLI were difficult to study for many years, because mutants lacking expression have many developmental deficits including lack of a diencephalon
. Explant
and lineage-labeling experiments previously described aided in elucidation of the role of shh
and other genes in differentiation of these tissues
.
s (at a precise stage
yet to be fully determined), the ZLI and its lineage restriction disappears, allowing cells to migrate across the former boundary and the dorsal
and ventral thalami
to merge into one functional unit, as shown by replication-incompetent retroviral
experiments that marked cells and showed their migration throughout the diencephalon.
has been shown to induce expression
of thalamic
and prethalamic
markers
, gbx2 and dlx2
/ nkx2.1, respectively. This differential induction most likely is due to the expression of genes such as irx3 in the thalamus
: ectopic expression
experiments showed that if irx3, which is normally expressed in the developing thalamus
, is expressed anterior to the ZLI, then the developing prethalamus
will change identity. Note that these genes which help confer shh
competence help to pattern the ZLI.
Signaling from the ZLI cooperating with thalamic
and prethalamic
markers
ensures the migration of post-mitotic (neural progenitor) cells to the mantle zone where the cells assemble into nuclei
characteristic of the thalamus
. These nuclei
are the mechanism of the relay of information from the thalamus
to the cortex
. The thalamus
itself is highly diverse, with each nucleus
having distinct morphologies
and physiologies according to the region of the brain
to which it is connected. These differences are thought to originate in differential gene expression
in the thalamus
and prethalamus
, which allows for a single structure with multiple different and separate functions once the two have merged and completed growth and differentiation. So an functional interplay between Shh from the ZLI and the bHLH factor Her6 (homolog to HES1
) determines the neuronal identity within the thalamus: Her6 positive cells in the prethalamus
and rostral thalamus
differentiate into GABA
ergic inhibitory neurons, whereas her negative cells become glutamatergic relay neurons. Both cell types depend on Shh signal as trigger to initiate the developmental programme.
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
forebrain (which is analogous to the human cerebrum) that serves as a signaling center and a restrictive border between the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
(also known as the dorsal thalamus) and the prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
(ventral thalamus). Sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
(shh) signaling from the ZLI is crucial in the development of the diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
, which develops into the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, the pretectum
Pretectum
The pretectum, also known as the pretectal area, is a region of neurons found between the thalamus and midbrain. It receives binocular sensory input from retinal ganglion cells of the eyes, and is the region responsible for maintaining the pupillary light reflex.-Outputs:The pretectum, after...
, and the anterior tegmental
Ventral tegmentum
The ventral tegmentum , better known as the ventral tegmental area , is a group of neurons located close to the midline on the floor of the midbrain...
structures. The ZLI together with the prethalamus and thalamus make up the mid-diencephalic territory (MDT).
Discovery
Cell lineage restriction boundaries, across which replicating cells cannot migrate, were first discovered in invertebrateInvertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s, where the expression of various Hox genes in each compartment confer the differentiation of observable segments in the adult body of Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
. Analogous structures were discovered in the developing vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Rhombomere
Rhombomere
In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the...
s, which extend down the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
from the hindbrain, contain clear boundaries and each express various Hox genes that are necessary for differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
of structures within the body. More anterior regions of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
were examined in search of other cell lineage restriction boundaries, and multiple potential boundaries continue to be studied (see Developmental Boundaries).
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
influence surrounding tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, was elucidated by first observing differential expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of Hox genes in various compartments and second by observing mutant D. melanogaster
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
and corresponding phenotypic
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
(physical) changes.
The ZLI was first discovered in the chick
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
using explant
Explant culture
In biology, explant culture is a technique used for the isolation of cells from a piece or pieces of tissue. Tissue harvested in this manner is called an explant...
and lineage-labeling experiments. In the explant experiments, cells in the region that will become the ZLI, the prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
, and the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
in the chick were removed and placed into separate cultures
Explant culture
In biology, explant culture is a technique used for the isolation of cells from a piece or pieces of tissue. Tissue harvested in this manner is called an explant...
; the cells continued to grow and retained their identity (the ZLI began transcribing
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, whereas the prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
and thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
did not). Necessity of the ZLI and its corresponding ' expression were evidenced by lack of thalamic and prethalamic genetic markers in culture (see Signaling). These experiments confirmed the ZLI as a signaling center. In lineage-labeling experiments, cells were genetically marked, so that each time a labeled cell replicated, its progeny
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
were marked as well. Cells that were marked in the developing ZLI and their progeny remained restricted to the zone. These experiments demonstrated the ZLI as a cell-lineage restriction boundary.
Not only a boundary, the ZLI is also a compartment with separate cell lineage restriction boundaries both anterior and posterior of a section of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression. The importance of the ZLI was once more confirmed by ectopic expression
Ectopic expression
Ectopic expression is the expression of a gene in an abnormal place in an organism. This can be caused by a disease, or it can be artificially produced as a way to help determine what the function of that gene is....
of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
in other regions of the forebrain, known as the prosencephalon
Prosencephalon
In the anatomy of the brain of vertebrates, the prosencephalon is the rostral-most portion of the brain. The prosencephalon, the mesencephalon , and rhombencephalon are the three primary portions of the brain during early development of the central nervous system...
during development (both the telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
and diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
), inducing a ZLI-like region that induces thalamic fate.
Developmental Boundaries
During developmentDevelopmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
in both vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s, cell lineage restriction boundaries and signaling centers are formed in order to ensure proper differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
of the body. Chemical signals
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
, like shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
from the ZLI, are often released from these boundaries and compartments in a concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
gradient (the chemicals are in much higher concentrations closer to the source) and confer identity to flanking regions. Other genes differentially expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in these flanking regions aid in ensuring proper differentiation (see Signaling).
Rhombomere
In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the...
, serves as an independent compartment that confers the identity of diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
in anterior and posterior regions. Other developmental boundaries serve as cell-lineage restriction boundaries but not signaling centers, while others are signaling centers to and from which cells can migrate. Despite discoveries of cell lineage restriction boundaries and compartments in the brain, many of the regions studied have been disproven as segmental boundaries. These areas have potential as signaling centers, which have influence over the development of neighboring tissues.
These boundaries have great influence over other regions of the brain: the placement of the ZLI not only affects the size of adjacent regions but also the size of the telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
. A posterior shift in the ZLI allows more cells to be allocated to the telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
. The same is true for other developmental boundaries in the brain and throughout the body: shifts in boundaries responsible for allocating a certain amount of tissue to a certain function result in drastic changes in the adult structure. These boundaries are of crucial importance for proper differentiation.
Initial Axis Patterning
After gastrulationGastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
, the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
is completely undifferentiated
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
and requires many different cues to initiate proper differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
of the body. The top (roof plate, on the dorsal side of the embryo) and bottom (floor plate, on the ventral side) play a crucial role in these first steps: each acts through global signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
(signaling throughout the entire embryo) for dorsoventral
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
neural patterning. After completion of the development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
of the dorsoventral
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
axis, more local signaling occurs in the developing brain: developmental boundaries such as the midbrain-hindbrain boundary (MHB), rhombomere
Rhombomere
In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the...
s, and the ZLI aid in anteroposterior
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
organization.
Emergence of Shh Expression
Shortly after the beginnin dorsoventralAnatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
patterning, shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
is expressed along the basal plate
Basal plate (neural tube)
In the developing nervous system, the basal plate is the region of the neural tube ventral to the sulcus limitans. It extends from the rostral mesencephalon to the end of the spinal cord and contains primarily motor neurons, whereas neurons found in the alar plate are primarily associated with...
(the bottom) of the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
, which functions in “ventralization
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
of the neural tube
Neural tube
In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord...
, promotion of growth and proliferation
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
, and formation of the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
”. As the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
continues to develop
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression characteristic of the ZLI extends dorsally
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
to form a wedge that eventually narrows to a strip at approximately 22 somite
Somite
A somite is a division of the body of an animal. In vertebrates this is mainly discernible in the embryo stage; in arthropods it is a characteristic of a hypothetical ancestor.- In vertebrates :...
s (the number of developed rhombomere
Rhombomere
In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the...
s) or less than one day in zebrafish. Although shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression extends dorsally
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
from the basal plate
Basal plate (neural tube)
In the developing nervous system, the basal plate is the region of the neural tube ventral to the sulcus limitans. It extends from the rostral mesencephalon to the end of the spinal cord and contains primarily motor neurons, whereas neurons found in the alar plate are primarily associated with...
, the ZLI is capable of forming even without the basal plate
Neural tube
In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord...
or mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
al tissue. Shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
cooperates with dlx2
Dlx (gene)
Dlx is a family of homeodomain transcription factors which are related to the Drosophila distal-less gene .The family has been related to a number of developmental features.The family seems to be well preserved across species....
and fezl anteriorly
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
and irx3 and dbx1a posteriorly (genes expressed vary among different organisms), which are gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s that are expressed in the prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
and thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, respectively.
The ZLI is also characterized by a lack of lunatic fringe
Lunatic Fringe
Lunatic fringe is a term used to characterize members of a usually political or social movement espousing extreme, eccentric, or fanatical views. It was coined by the 26th President of the United States, Theodore Roosevelt , to describe some American anarchists, especially those who engaged in...
(lfng), which is observable even before shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression is observed in the forming ZLI. This indicates that cells are fated for ZLI formation before induction by shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
(n.b. shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
signals from the ZLI and is characteristic of the compartment during and after formation). Lfng
Lunatic Fringe
Lunatic fringe is a term used to characterize members of a usually political or social movement espousing extreme, eccentric, or fanatical views. It was coined by the 26th President of the United States, Theodore Roosevelt , to describe some American anarchists, especially those who engaged in...
is expressed very early (soon after gastrulation
Gastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
) in the region that will become the ZLI, but shortly thereafter expression recedes through migration of lfng
Lunatic Fringe
Lunatic fringe is a term used to characterize members of a usually political or social movement espousing extreme, eccentric, or fanatical views. It was coined by the 26th President of the United States, Theodore Roosevelt , to describe some American anarchists, especially those who engaged in...
-expressing cells to form the lfng
Lunatic Fringe
Lunatic fringe is a term used to characterize members of a usually political or social movement espousing extreme, eccentric, or fanatical views. It was coined by the 26th President of the United States, Theodore Roosevelt , to describe some American anarchists, especially those who engaged in...
-free wedge characteristic of the developing ZLI. Shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression does not extend dorsally
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
until a few hours later.
Positioning
The factors influencing the formation and location of the ZLI are widely studied but still disputed. Differences between different animal modelAnimal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
s further complicate elucidation of the pathways
Genetic pathway
A genetic pathway is the set of interactions occurring between a group of genes who depend on each other's individual functions in order to make the aggregate function of the network available to the cell...
, specifically between chicks/ mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian models and zebrafish.
Wnt
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
(the family wingless) genes are crucial for the development of the ZLI both directly and indirectly in all animal systems. Along with the role of Wnt
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
genes in patterning the anteroposterior
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
axis through gradient polarization, Wnt8b
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
is expressed within the ZLI itself and may help guide dorsal
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
movement of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression. The Wnt
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
polarization gradient has been linked to induction of ZLI-patterning genes irx3 and six3
SIX3
Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.-Interactions:SIX3 has been shown to interact with TLE1 and Neuron-derived orphan receptor 1.-External links:*...
, which border the ZLI posteriorly
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
and anteriorly
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
, respectively. However, these gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s have been shown to be non-essential for ZLI formation in zebrafish and have been reevaluated in other models.
Specification of the ZLI may also involve the ventral tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
of the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
: the prechordal
Prechordal plate
In the development of vertebrate animals, the prechordal plate is a "uniquely thickened portion" of the endoderm that is in contact with ectoderm immediately rostral to the cephalic tip of the notochord. It is the most likely origin of the rostral cranial mesoderm....
and epichordal plates, or neuroepithelial tissue (see figure). Interactions between these tissues may be responsible for the recession of expression of lfng
Lunatic Fringe
Lunatic fringe is a term used to characterize members of a usually political or social movement espousing extreme, eccentric, or fanatical views. It was coined by the 26th President of the United States, Theodore Roosevelt , to describe some American anarchists, especially those who engaged in...
which allows dorsal
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
movement shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression. The specific prechrodal and epichordal plates, characterized by expression of six3
SIX3
Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.-Interactions:SIX3 has been shown to interact with TLE1 and Neuron-derived orphan receptor 1.-External links:*...
and irx3, respectively, may influence positioning of the ZLI more so than the genes themselves. The prechrodal plate ventrally borders the telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
, with the epichrodal plate posterior
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
to it.
Studies of the formation of the ZLI performed in zebrafish have revealed the significance of otx2 and irx1 in ZLI positioning. Otx2 expression characterizes the developing optic tectum
Superior colliculus
The optic tectum or simply tectum is a paired structure that forms a major component of the vertebrate midbrain. In mammals this structure is more commonly called the superior colliculus , but, even in mammals, the adjective tectal is commonly used. The tectum is a layered structure, with a...
, which is responsible for sight processing. Expression extends anteriorly
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
and ends sharply at the ZLI, with high expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
along the line where shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
is expressed. Before the ZLI is formed, otx2 is expressed ubiquitously throughout the forebrain, and begins to recede to the position of the putative ZLI. Experiments where otx2 expression was repressed showed no dorsal
Dorsum (biology)
In anatomy, the dorsum is the upper side of animals that typically run, fly, or swim in a horizontal position, and the back side of animals that walk upright. In vertebrates the dorsum contains the backbone. The term dorsal refers to anatomical structures that are either situated toward or grow...
movement of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
expression and no ZLI formation. Irx1, which is analogous to irx3 in birds and mammals, is expressed posterior to the ZLI. Studies have suggested that while otx2 positively restricts the ZLI anteriorly (shh
SHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
cannot be expressed where otx2 is not), irx1 negatively restricts the ZLI posteriorly. Other genes crucial for differentiation in the brain, including Fgf genes responsible for patterning of the midbrain-hindbrain boundary (MHB), have been implicated in positioning of the ZLI.
Studies on the role of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
signaling in the ZLI were difficult to study for many years, because mutants lacking expression have many developmental deficits including lack of a diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
. Explant
Explant culture
In biology, explant culture is a technique used for the isolation of cells from a piece or pieces of tissue. Tissue harvested in this manner is called an explant...
and lineage-labeling experiments previously described aided in elucidation of the role of shh
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
and other genes in differentiation of these tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
Differentiation After ZLI Degradation
After differentiation of the progenitor cellProgenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
s (at a precise stage
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
yet to be fully determined), the ZLI and its lineage restriction disappears, allowing cells to migrate across the former boundary and the dorsal
Dorsum (biology)
In anatomy, the dorsum is the upper side of animals that typically run, fly, or swim in a horizontal position, and the back side of animals that walk upright. In vertebrates the dorsum contains the backbone. The term dorsal refers to anatomical structures that are either situated toward or grow...
and ventral thalami
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
to merge into one functional unit, as shown by replication-incompetent retroviral
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
experiments that marked cells and showed their migration throughout the diencephalon.
Signaling
After establishment of the ZLI, shhSHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
has been shown to induce expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of thalamic
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and prethalamic
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
markers
Genetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
, gbx2 and dlx2
Dlx (gene)
Dlx is a family of homeodomain transcription factors which are related to the Drosophila distal-less gene .The family has been related to a number of developmental features.The family seems to be well preserved across species....
/ nkx2.1, respectively. This differential induction most likely is due to the expression of genes such as irx3 in the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
: ectopic expression
Ectopic expression
Ectopic expression is the expression of a gene in an abnormal place in an organism. This can be caused by a disease, or it can be artificially produced as a way to help determine what the function of that gene is....
experiments showed that if irx3, which is normally expressed in the developing thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, is expressed anterior to the ZLI, then the developing prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
will change identity. Note that these genes which help confer shh
SHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
competence help to pattern the ZLI.
Signaling from the ZLI cooperating with thalamic
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and prethalamic
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
markers
Genetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
ensures the migration of post-mitotic (neural progenitor) cells to the mantle zone where the cells assemble into nuclei
Nucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
characteristic of the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
. These nuclei
Nucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
are the mechanism of the relay of information from the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
to the cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
. The thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
itself is highly diverse, with each nucleus
Nucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
having distinct morphologies
Morphology (biology)
In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....
and physiologies according to the region of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
to which it is connected. These differences are thought to originate in differential gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
, which allows for a single structure with multiple different and separate functions once the two have merged and completed growth and differentiation. So an functional interplay between Shh from the ZLI and the bHLH factor Her6 (homolog to HES1
HES1
Transcription factor HES-1 is a protein that in humans is encoded by the HES1 gene.-Interactions:HES1 has been shown to interact with TLE2 and Sirtuin 1.- External links :...
) determines the neuronal identity within the thalamus: Her6 positive cells in the prethalamus
Prethalamus
The prethalamus or subthalamus is part of the diencephalon and therefore part of the brain.Developmental biologists prefer the term prethalamus, as it can be genetically defined , whereas anatomists often use the expression subthalamus.The prethalamus is part of the mid-diencephalic territory...
and rostral thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
differentiate into GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
ergic inhibitory neurons, whereas her negative cells become glutamatergic relay neurons. Both cell types depend on Shh signal as trigger to initiate the developmental programme.