Neuroepithelial cell
Encyclopedia
Neuroepithelial cells are the "stem cells" of the nervous system, deriving from actual stem cells in several different stages of development and differentiating further into multiple types of cells. They appear during embryonic development of the neural tube
as well as in adult neurogenesis
in specific areas of the central nervous system
and are associated with several neurodegenerative diseases. These cells, often have also been called neuroblast
s in an effort to delineate them as precursors to neurons and glial cells.
begin multiplying rapidly and fold in forming the neural plate
, which invaginates during the fourth week of embryonic growth and forms the neural tube
. The formation of the neural tube
polarizes the neuroepithelial cells by orienting the apical side of the cell to face inward, which later becomes the ventricular zone, and the basal side is oriented outward, which contacts the pial
, or outer surface of the developing brain
. As part of this polarity, neuroepithelial cells express prominin-1
in the apical plasma membrane as well as tight junctions to maintain the cell polarity. Integrin
α6 anchors the neuroepithelial cells to the basal lamina
. The neural tube
begins as a single layer of pseudostratified epithelial cells, but rapid proliferation of neuroepithelial cells creates additional layers and eventually three distinct regions of growth. As these additional layers form the apical-basal polarity must be downregulated. Further proliferation of the cells in these regions gives rise to three distinct areas of the brain: the forebrain, midbrain, and hindbrain. The neural plate
itself eventually gives rise to the spinal cord
.
Neuroepithelial cells are a class of stem cell
and have similar characteristics, most notably the ability to self renew. During the formation of the neural tube
, neuroepithelial cells undergo symmetric proliferative divisions that give rise to two new neuroepithelial cells. At a later stage of brain development, neuroepithelial cells begin to self renew and give rise to non-stem cell progenitors, such as radial glial cells simultaneously by undergoing asymmetric division. Expression of Tis21, an antiproliferative gene, causes the neuroepithelial cell to make the switch from proliferative division to neuronic division. Many of the neuroepithelial cells also divide into radial glial cells, a similar, but more fate restricted cell. Being a more fate restricted cell the radial glial cell will either generate postmitotic neurons, intermediate progenitor cells, or astrocytes in gliogenesis
. During neuroepithelial cell division, interkinetic nuclear migration allows the cells to divide unrestricted while maintaining a dense packing. During G1
the cell nucleus
migrates to the basal side of the cell and remains there for S phase
and migrates to the apical side for G2 phase
. This migration requires the help of microtubules and actin filaments.
neuroepithelial cells stop expressing occludin
, a tight junction
protein. Loss of occludin causes a loss of the previous tight junction seal which is required for the generation of nonepithelial cells such as neurons. Another tight junction
protein, PAR3, remains at the apical side of the cell co-localizing with N-cadherin and keeps the apical face of the neuroepithelial cell intact. In the absence of occludin
some polarity is still lost and the neuroepithelial cell gives rise to the radial glial cell.
(SVZ) and the dentate gyrus
of the hippocampus
. These cells do not appear in any of the peripheral nervous system
. Often categorized as neural stem cells, neuroepithelial cells give rise to only a few varieties of neural cells, making them multipotent
- a definite distinction from the pluripotent
stem cells found in embryonic development. Neuroepithelial cells undergo mitosis generating more neuroepithelial cells, radial glial cells or progenitor cells, the latter two differentiating into either neurons or glial cells. The neuroepithelial cells undergo two different forms of mitosis: asymmetric differentiating division and symmetric prolific division. The asymmetric cell division
results in two different varieties of daughter cells (i.e. a neuroepithelial cell divides into a radial glial cell and another neuroepithelial cell), while the symmetric version yields identical daughter cells. This effect is caused by the orientation of the mitotic spindle
, which is located in either the posterior or anterior area of the mitotic cell, rather than the center where it is found during symmetric dividion. The progenitor cells and radial glial cells respond to extracellular trophic factors - like ciliary neurotrophic factor
(CNTF), cytokines or neuregulin 1
(NGR1) - that can determine whether the cells will differentiate into either neurons or glia.
, Alzheimer's disease
, epilepsy
and even Parkinson's disease
. While adult neurogenesis is up-regulated in the hippocampus in patients with these diseases, whether its effects are regenerative or inconclusive remains to be seen.
Neurogenesis is also associated with neuroplasticity
in a complementary fashion. The new neurons generated by the neuroepithelial cells, progenitors and radial glial cells will not survive unless they are able to integrate into the system by making connections with new neighbors. This also leads to many controversial concepts, like neurogenic therapy involving the transplant of local progenitor cells to a damaged area.
, develop in individuals between the ages of 20-50 and is relatively rare in individuals under the age of twenty. The cysts are benign tumors that usually appear in the anterior third ventricle
. The cysts occur in the epithelium putting their patients at risk for obstructive hydrocephalus
, increased intracranial pressure
, and rarely intracystic hemorrhage. This results from the cysts enlarging by causing the epithelium to secrete additional mucinous fluid. The cysts are usually found incidentally or if patients become symptomatic presenting with the symptoms of hydrocephalus. The larger cysts are operated on while smaller cysts that are not obstructive can be left alone .
manifest in glial cells, which are responsible for supporting and protecting nerve cells in the brain. The tumor develops over oligodendrocytes and is usually found in the cerebrum around the frontal
or temporal
lobes. The tumors can either grow slowly in a well-differentiated manner delaying the onset of symptoms, or they can grow rapidly to form an anaplastic
oligodendroglioma
. The symptoms for this type of tumor include headaches and visual problems. Additionally, blockage of ventricles could cause build up of cerebral spinal fluid resulting in swelling around the tumor. The location of the tumor may also affect the symptoms since frontal lobe tumors can cause gradual mood or personality changes while temporal lobe tumors result in coordination and speech problems .
by combining neurons that developed from embryonic stem cells with glial cells that were also derived from embryonic stem cells. These neural chimeras give researchers a comprehensive way of studying the molecular mechanisms behind cell repair and regeneration via neuroepithelial precursor cells and will hopefully shed light on possible nervous system repair in a clinical setting. In an attempt to identify the key features that differentiate neuroepithelial cells from their progenitor cells
, researchers identified an intermediate filament
that was expressed by 98% of the neuroepithelial cells of the neural tube, but none of their progenitor cells. After this discovery it became clear that all three cell types in the nervous system resulted from a homogenous population of stem cells. In order make clinical neural repair possible researchers needed to further characterize regional determination of stem cells during brain development by determining what factors commit a precursor to becoming one or the other. While the exact factors that lead to differentiation are unknown, researchers have taken advantage of human-rat neural chimeras to explore the development of human neurons and glial cells in an animal model. These neural chimeras have permitted researchers to look at neurological diseases in an animal model where traumatic and reactive changes can be controlled. Eventually researchers hope to be able to use the information taken from these neural chimera experiments to repair regions of the brain affected by central nervous system disorders. The problem of delivery, however, has still not been resolved as neural chimeras have been shown to circulate throughout the ventricles and incorporate into all parts of the CNS. By finding environmental cues of differentiation, neuroepithelial precursor transplantation could be used in the treatment of many diseases including multiple sclerosis
, Huntington’s disease, and Parkinson’s disease. Further exploration of neural chimera cells and chimeric brains will provide evidence for manipulating the correct genes and increasing the efficacy of neural transplant repair.
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...
as well as in adult neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
in specific areas of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and are associated with several neurodegenerative diseases. These cells, often have also been called neuroblast
Neuroblast
A neuroblast is a dividing cell that will develop into neurons or glia. The characterisation of neuroblasts and their development in Drosophila melanogaster was widely achieved by Chris Doe, Corey Goodman and Mike Bate. In humans, neuroblasts produced by stem cells in the adult subventricular zone...
s in an effort to delineate them as precursors to neurons and glial cells.
Brain development
During the third week of embryonic growth the brain begins to develop in the early fetus in a process called induction. Neuroepithelial cells of the ectodermEctoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
begin multiplying rapidly and fold in forming the neural plate
Neural plate
In human embryology, formation of neural plate is the first step of neurulation. It is created by a flat thickening opposite to the primitive streak of the ectoderm.-Development:...
, which invaginates during the fourth week of embryonic growth and forms 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...
. The formation 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...
polarizes the neuroepithelial cells by orienting the apical side of the cell to face inward, which later becomes the ventricular zone, and the basal side is oriented outward, which contacts the pial
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
, or outer surface of the developing 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,...
. As part of this polarity, neuroepithelial cells express prominin-1
CD133
CD133, originally known as AC133. CD133 is a glycoprotein also known in humans and rodents as Prominin 1 . Currently the function of CD133 is unknown...
in the apical plasma membrane as well as tight junctions to maintain the cell polarity. Integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
α6 anchors the neuroepithelial cells to the basal lamina
Basal lamina
The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often confused with the basement membrane, and sometimes used inconsistently in the literature, see below....
. 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...
begins as a single layer of pseudostratified epithelial cells, but rapid proliferation of neuroepithelial cells creates additional layers and eventually three distinct regions of growth. As these additional layers form the apical-basal polarity must be downregulated. Further proliferation of the cells in these regions gives rise to three distinct areas of the brain: the forebrain, midbrain, and hindbrain. The neural plate
Neural plate
In human embryology, formation of neural plate is the first step of neurulation. It is created by a flat thickening opposite to the primitive streak of the ectoderm.-Development:...
itself eventually gives rise to the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
.
Neuroepithelial cell proliferation
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
and have similar characteristics, most notably the ability to self renew. During the formation 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...
, neuroepithelial cells undergo symmetric proliferative divisions that give rise to two new neuroepithelial cells. At a later stage of brain development, neuroepithelial cells begin to self renew and give rise to non-stem cell progenitors, such as radial glial cells simultaneously by undergoing asymmetric division. Expression of Tis21, an antiproliferative gene, causes the neuroepithelial cell to make the switch from proliferative division to neuronic division. Many of the neuroepithelial cells also divide into radial glial cells, a similar, but more fate restricted cell. Being a more fate restricted cell the radial glial cell will either generate postmitotic neurons, intermediate progenitor cells, or astrocytes in gliogenesis
Gliogenesis
Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells.-Overview:Gliogenesis results in the formation of non-neuronal glia populations derived from multipotent neural stem cells. In this capacity, glial cells provide multiple functions to both the...
. During neuroepithelial cell division, interkinetic nuclear migration allows the cells to divide unrestricted while maintaining a dense packing. During G1
G1 phase
The G1 phase is a period in the cell cycle during interphase, before the S phase. For many cells, this phase is the major period of cell growth during its lifespan. During this stage new organelles are being synthesized, so the cell requires both structural proteins and enzymes, resulting in great...
the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
migrates to the basal side of the cell and remains there for S phase
S phase
S-phase is the part of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Precise and accurate DNA replication is necessary to prevent genetic abnormalities which often lead to cell death or disease. Due to the importance, the regulatory pathways that govern this...
and migrates to the apical side for G2 phase
G2 phase
G2 phase is the 3rd and final subphase of Interphase in the cell cycle directly preceding Mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated...
. This migration requires the help of microtubules and actin filaments.
Radial glial cell switch
Neuroepithelial cells give rise to radial glial cells early on during embryonic development. To make the switch, neuroepithelial cells begin downregulating their epithelial features. During neurulationNeurulation
Neurulation is the stage of organogenesis in vertebrate embryos, during which the neural tube is transformed into the primitive structures that will later develop into the central nervous system....
neuroepithelial cells stop expressing occludin
Occludin
Occludin is a protein that in humans is encoded by the OCLN gene.Occludin is a 65-kDa integral plasma-membrane protein located at the tight junctions, described for the first time in 1993 by Shoichiro Tsukita...
, a tight junction
Tight junction
Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates...
protein. Loss of occludin causes a loss of the previous tight junction seal which is required for the generation of nonepithelial cells such as neurons. Another tight junction
Tight junction
Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates...
protein, PAR3, remains at the apical side of the cell co-localizing with N-cadherin and keeps the apical face of the neuroepithelial cell intact. In the absence of occludin
Occludin
Occludin is a protein that in humans is encoded by the OCLN gene.Occludin is a 65-kDa integral plasma-membrane protein located at the tight junctions, described for the first time in 1993 by Shoichiro Tsukita...
some polarity is still lost and the neuroepithelial cell gives rise to the radial glial cell.
Genesis of neuroepithelial cells in the adult CNS
In the adult CNS, neuroepithelial cells arise in several different areas of the brain: the subventricular zoneSubventricular zone
The subventricular zone is a paired brain structure situated throughout the lateral walls of the lateral ventricles. It has been associated with having four distinct layers of variable thickness and cell density, as well as cellular composition....
(SVZ) and the dentate gyrus
Dentate gyrus
The dentate gyrus is part of the hippocampal formation. It is thought to contribute to new memories as well as other functional roles. It is notable as being one of a select few brain structures currently known to have high rates of neurogenesis in adult rats, .The dentate gyrus cells receive...
of the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. These cells do not appear in any of the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
. Often categorized as neural stem cells, neuroepithelial cells give rise to only a few varieties of neural cells, making them multipotent
Cell potency
The potency of a cell specifies its differentiation potential, or potential to differentiate into different cell types.-Totipotency:Totipotency is the ability of a single cell to divide and produce all the differentiated cells in an organism, including extraembryonic tissues.Totipotent cells...
- a definite distinction from the pluripotent
Cell potency
The potency of a cell specifies its differentiation potential, or potential to differentiate into different cell types.-Totipotency:Totipotency is the ability of a single cell to divide and produce all the differentiated cells in an organism, including extraembryonic tissues.Totipotent cells...
stem cells found in embryonic development. Neuroepithelial cells undergo mitosis generating more neuroepithelial cells, radial glial cells or progenitor cells, the latter two differentiating into either neurons or glial cells. The neuroepithelial cells undergo two different forms of mitosis: asymmetric differentiating division and symmetric prolific division. The asymmetric cell division
Asymmetric cell division
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to normal, symmetric, cell divisions, which give rise to daughter cells of equivalent fates...
results in two different varieties of daughter cells (i.e. a neuroepithelial cell divides into a radial glial cell and another neuroepithelial cell), while the symmetric version yields identical daughter cells. This effect is caused by the orientation of the mitotic spindle
Mitotic spindle
In cell biology, the spindle fibers are the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells...
, which is located in either the posterior or anterior area of the mitotic cell, rather than the center where it is found during symmetric dividion. The progenitor cells and radial glial cells respond to extracellular trophic factors - like ciliary neurotrophic factor
Ciliary neurotrophic factor
Ciliary neurotrophic factor is a protein that in humans is encoded by the CNTF gene.CNTF has also been shown to be expressed by cells on the bone surface, and to reduce the activity of bone forming cells, osteoblasts.- Satiety effects :...
(CNTF), cytokines or neuregulin 1
Neuregulin 1
Neuregulin 1 or NRG1 is a protein which in humans is encoded by the NRG1 gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in numerous isoforms by alternative splicing, which allows it to perform a wide variety of functions...
(NGR1) - that can determine whether the cells will differentiate into either neurons or glia.
Neurogenesis in neural repair
Neurogenesis in the adult brain is often associated with diseases that deteriorate the CNS, like Huntington's diseaseHuntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
and even Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. While adult neurogenesis is up-regulated in the hippocampus in patients with these diseases, whether its effects are regenerative or inconclusive remains to be seen.
Neurogenesis is also associated with neuroplasticity
Neuroplasticity
Neuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
in a complementary fashion. The new neurons generated by the neuroepithelial cells, progenitors and radial glial cells will not survive unless they are able to integrate into the system by making connections with new neighbors. This also leads to many controversial concepts, like neurogenic therapy involving the transplant of local progenitor cells to a damaged area.
Dysembryoplastic neuroepithelial tumor (DNT)
Dysembryoplastic Neuroepithelial Tumors are a rare, benign tumor that affects children and teenagers under the age of twenty. The tumor occurs in the tissue covering the brain and spinal chord. The symptoms of the tumor are dependent on its location, but most children experience seizures that cannot be controlled by medication. DNT is usually treated through invasive surgery and the long term outlook for patients is generally good .Neuroepithelial cysts
Neuroepithelial cysts, also known as colloid cystsColloid cyst
A colloid cyst is a cyst containing gelatinous material in the brain. It is almost always found just posterior to the foramen of Monro in the anterior aspect of the third ventricle, originating from the roof of the ventricle. Because of its location, it can cause obstructive hydrocephalus and...
, develop in individuals between the ages of 20-50 and is relatively rare in individuals under the age of twenty. The cysts are benign tumors that usually appear in the anterior third ventricle
Third ventricle
The third ventricle is one of four connected fluid-filled cavities comprising the ventricular system within the human brain. It is a median cleft between the two thalami, and is filled with cerebrospinal fluid ....
. The cysts occur in the epithelium putting their patients at risk for obstructive hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
, increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, and rarely intracystic hemorrhage. This results from the cysts enlarging by causing the epithelium to secrete additional mucinous fluid. The cysts are usually found incidentally or if patients become symptomatic presenting with the symptoms of hydrocephalus. The larger cysts are operated on while smaller cysts that are not obstructive can be left alone .
Oligodendroglial tumors
Oligodendroglial tumorsOligodendroglioma
Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. They occur primarily in adults but are also found in children...
manifest in glial cells, which are responsible for supporting and protecting nerve cells in the brain. The tumor develops over oligodendrocytes and is usually found in the cerebrum around the frontal
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
or temporal
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
lobes. The tumors can either grow slowly in a well-differentiated manner delaying the onset of symptoms, or they can grow rapidly to form an anaplastic
Anaplasia
Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms . Sometimes, the term also includes an increased capacity for multiplication. Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to...
oligodendroglioma
Oligodendroglioma
Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. They occur primarily in adults but are also found in children...
. The symptoms for this type of tumor include headaches and visual problems. Additionally, blockage of ventricles could cause build up of cerebral spinal fluid resulting in swelling around the tumor. The location of the tumor may also affect the symptoms since frontal lobe tumors can cause gradual mood or personality changes while temporal lobe tumors result in coordination and speech problems .
Neural chimeras
Researchers have been able to create neural chimerasChimera (genetics)
A chimera or chimaera is a single organism that is composed of two or more different populations of genetically distinct cells that originated from different zygotes involved in sexual reproduction. If the different cells have emerged from the same zygote, the organism is called a mosaic...
by combining neurons that developed from embryonic stem cells with glial cells that were also derived from embryonic stem cells. These neural chimeras give researchers a comprehensive way of studying the molecular mechanisms behind cell repair and regeneration via neuroepithelial precursor cells and will hopefully shed light on possible nervous system repair in a clinical setting. In an attempt to identify the key features that differentiate neuroepithelial cells from their progenitor cells
Progenitor 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...
, researchers identified an intermediate filament
Intermediate filament
Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...
that was expressed by 98% of the neuroepithelial cells of the neural tube, but none of their progenitor cells. After this discovery it became clear that all three cell types in the nervous system resulted from a homogenous population of stem cells. In order make clinical neural repair possible researchers needed to further characterize regional determination of stem cells during brain development by determining what factors commit a precursor to becoming one or the other. While the exact factors that lead to differentiation are unknown, researchers have taken advantage of human-rat neural chimeras to explore the development of human neurons and glial cells in an animal model. These neural chimeras have permitted researchers to look at neurological diseases in an animal model where traumatic and reactive changes can be controlled. Eventually researchers hope to be able to use the information taken from these neural chimera experiments to repair regions of the brain affected by central nervous system disorders. The problem of delivery, however, has still not been resolved as neural chimeras have been shown to circulate throughout the ventricles and incorporate into all parts of the CNS. By finding environmental cues of differentiation, neuroepithelial precursor transplantation could be used in the treatment of many diseases including multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, Huntington’s disease, and Parkinson’s disease. Further exploration of neural chimera cells and chimeric brains will provide evidence for manipulating the correct genes and increasing the efficacy of neural transplant repair.