Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of 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,...

 development and to address the underlying mechanisms. The field draws on both neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...

 and developmental biology
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...

 to provide insight into the cellular and molecular mechanisms by which complex nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

s develop. Defects in neural development can lead to cognitive, motor, and intellectual disability, as well as neurological disorders such as autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...

, Rett syndrome
Rett syndrome
Rett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...

, and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...


Overview of brain development

The brain emerges during embryonic development from the neural tube, an early embryonic structure. The most anterior part of the neural tube is called the telencephalon, which expands rapidly due to cell proliferation, and eventually gives rise to the brain. Gradually some of the cells stop dividing and differentiate into neurons and glial cells, which are the main cellular components of the brain. The newly generated neurons migrate to different parts of the developing brain to self-organize into different brain structures. Once the neurons have reached their regional positions, they extend axons and dendrites, which allow them to communicate with other neurons via synapses. Synaptic communication between neurons leads to the establishment of functional neural circuits that mediate sensory and motor processing, and underlie behavior. The brain does most of its development within the first 20 years of life.

Aspects of neural development

Some landmarks of neural development include the birth and 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 neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s from stem cell precursors, the migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...

 of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

s and dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

s from neurons, guidance
Axon guidance
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...

 of the motile growth cone
Growth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...

 through the embryo towards postsynaptic partners, the generation of synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s between these axons and their postsynaptic partners, and finally the lifelong changes
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...

 in synapses, which are thought to underlie learning and memory.

Typically, these neurodevelopmental processes can be broadly divided into two classes: activity-independent mechanisms and activity-dependent mechanisms. Activity-independent mechanisms are generally believed to occur as hardwired processes determined by genetic programs played out within individual neurons. These include 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...

, migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...

 and axon guidance
Axon guidance
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...

 to their initial target areas. These processes are thought of as being independent of neural activity and sensory experience. Once axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

s reach their target areas, activity-dependent mechanisms come into play. Although synapse formation is an activity-independent event, modification of synapses and synapse elimination requires neural activity.

Developmental neuroscience uses a variety of animal models including mice Mus musculus , the fruit fly 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...

, the zebrafish Danio rerio
Danio rerio
The zebrafish, Danio rerio, is a tropical freshwater fish belonging to the minnow family of order Cypriniformes. It is a popular aquarium fish, frequently sold under the trade name zebra danio, and is an important vertebrate model organism in scientific research.-Taxonomy:The zebrafish are...

, Xenopus laevis tadpoles and the worm Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

, among others.

Neural induction

During early embryonic development the ectoderm becomes specified to give rise to the epidermis (skin) and the neural plate. The conversion of undifferentiated ectoderm to neuro-ectoderm requires signals from the mesoderm. At the onset of gastrulation presumptive mesodermal cells move through the dorsal blastopore lip and form a layer in between the endoderm and the ectoderm. These mesodermal cells that migrate along the dorsal midline give rise to a structure called the notochord. Ectodermal cells overlying the notochord develop into the neural plate in response to a diffusible signal produced by the notochord. The remainder of the ectoderm gives rise to the epidermis (skin). The ability of the mesoderm to convert the overlying ectoderm into neural tissue is called Neural Induction.

The neural plate folds outwards during the third week of gestation to form the neural groove
Neural groove
The neural groove is a shallow median groove between the neural folds of an embryo. The neural folds are two longitudinal ridges that are caused by a folding up of the ectoderm in front of the primitive streak of the developing embryo...

. Beginning in the future neck region, the neural folds
Neural folds
In front of the primitive streak two longitudinal ridges, caused by a folding up of the ectoderm, make their appearance, one on either side of the middle line...

 of this groove close to create 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 from the ectoderm is called Neurulation. The ventral part of the neural tube is called the basal plate
Basal plate
Basal plate may refer to:* Basal plate , the region of the neural tube ventral to the sulcus limitans* Basal plate , between this plate and the uterine muscular fibres are the stratum spongiosum and the boundary layer...

; the dorsal part is called the alar plate
Alar plate
The alar plate is a neural structure in the embryonic nervous system, part of the dorsal side of neural tube, that involves the communication of general somatic and general visceral sensory impulses. The caudal part later becomes sensory axon part of the spinal cord.-External links:* *...

. The hollow interior is called the neural canal. By the end of the fourth week of gestation, the open ends of the neural tube (the neuropores) close off.

Identification of neural inducers

A transplanted blastopore lip can convert ectoderm into neural tissue and is said to have an inductive effect. Neural Inducers are molecules that can induce the expression of neural genes in ectoderm explants without inducing mesodermal genes as well. Neural induction is often studied in Xenopus embryos since they have a simple body pattern and there are good markers to distinguish between neural and non-neural tissue. Examples of Neural Inducers are the molecules Noggin and Chordin.

When embryonic ectodermal cells are cultured at low density in the absence of mesodermal cells they undergo neural differentiation (express neural genes), suggesting that neural differentiation is the default fate of ectodermal cells. In explant cultures (which allow direct cell-cell interactions) the same cells differentiate into epidermis. This is due to the action of BMP4 (a TGF-β family protein) that induces ectodermal cultures to differentiate into epidermis. During neural induction, Noggin and Chordin are produced by the dorsal mesoderm (notochord) and diffuse into the overlying ectoderm to inhibit the activity of BMP4. This inhibition of BMP4 causes the cells to differentiate into neural cells.


Late in the fourth week, the superior part of the neural tube flexes at the level of the future midbrain—the mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....

. Above the mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....

 is the 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...

 (future forebrain) and beneath it is the rhombencephalon
The rhombencephalon is a developmental categorization of portions of the central nervous system in vertebrates.The rhombencephalon can be subdivided in a variable number of transversal swellings called rhombomeres...

 (future hindbrain).

The optical vesicle (which will eventually become the optic nerve, retina and iris) forms at the basal plate of the prosencephalon. The alar plate of the prosencephalon expands to form the cerebral hemispheres (the 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...

) whilst its basal plate becomes the 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...

. Finally, the optic vesicle grows to form an optic outgrowth.

Patterning of the nervous system

In chordates, dorsal ectoderm forms all neural tissue and the nervous system. Patterning occurs due to specific environmental conditions - different concentrations of signaling molecules

Dorsoventral axis
The ventral half of 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:...

 is controlled by the notochord
The notochord is a flexible, rod-shaped body found in embryos of all chordates. It is composed of cells derived from the mesoderm and defines the primitive axis of the embryo. In some chordates, it persists throughout life as the main axial support of the body, while in most vertebrates it becomes...

, which acts as the 'organiser'. The dorsal half is controlled by the ectoderm
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...

 plate which flanks the neural plate on either side.

Ectoderm follows a default pathway to become neural tissue. Evidence for this comes from single, cultured cells of ectoderm which go on to form neural tissue. This is postulated to be because of a lack of BMP
-In computing:* BMP file format, the file name extension for the Bitmap image file format.* Basic Multilingual Plane, related to the Unicode character set.* Beep Media Player, a multimedia player.-Biology:...

s, which are blocked by the organiser. The organiser may produce molecules such as follistatin
Follistatin also known as activin-binding protein is a protein that in humans is encoded by the FST gene. Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals....

, noggin and chordin
Chordin is a polypeptide that dorsalizes the developing embryo by binding ventralizing TGFβ proteins such as bone morphogenetic proteins. It may also play a role in organogenesis. There are five named isoforms of this protein that are produced by alternative splicing.In humans, the chordin peptide...

 which inhibit BMPs.

The ventral neural tube is patterned by 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) from the notochord, which acts as the inducing tissue. Notochord-derived Shh signals to the floor plate
Floor plate
The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions...

, and induces Shh expression in the floor plate. Floor plate-derived Shh subsequently signals to other cells in the neural tube, and is essential for proper specification of ventral neuron progenitor domains. Loss of Shh from the notochord and/or floor plate prevents proper specification of these progenitor domains. Shh binds Patched1, relieving Patched-mediated inhibition of Smoothened
Smoothened is a G protein-coupled receptor protein encoded by the gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine....

, leading to activation of Gli
GLI may refer to:* The Volkswagen GLI, a high performance version of the Volkswagen Jetta* Great Lakes Initiative, the fictional Marvel Comics superteam formerly known as the Great Lakes Avengers...

 family of transcription factors (Gli1, Gli2, and Gli3) transcription factors.

In this context Shh acts as a morphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...

 - it induces cell differentiation dependent on its concentration. At low concentrations it forms ventral interneurones, at higher concentrations it induces motor neuron development, and at highest concentrations it induces floor plate differentiation. Failure of Shh-modulated differentiation causes holoprosencephaly.

The dorsal neural tube is patterned by BMPs from the epidermal ectoderm flanking the neural plate. These induce sensory interneurones by activating Sr/Thr kinases and altering SMAD
SMAD may refer to:* Sowjetische Militäradministration in Deutschland* SMAD – proteins involved in cell signaling** R-SMAD – receptor regulated SMAD proteins** I-SMAD – inhibitory SMAD proteins...

 transcription factor levels.

Rostrocaudal (Anteroposterior) axis

Signals that control anteroposterior neural development include FGF and retinoic acid
Retinoic acid
Retinoic acid is a metabolite of vitamin A that mediates the functions of vitamin A required for growth and development. Retinoic acid is required in chordate animals which includes all higher animals from fishes to humans...

 which act in the hindbrain and spinal cord. The hindbrain, for example, is patterned by Hox genes, which are expressed in overlapping domains along the anteroposterior axis under the control of retinoic acid. The 3' genes in the Hox cluster are induced by retinoic acid in the hindbrain, whereas the 5' Hox genes are not induced by retinoic acid and are expressed more posteriorly in the spinal cord. Hoxb-1 is expressed in rhombomere 4 and gives rise to the facial nerve
Facial nerve
The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity...

. Without this Hoxb-1 expression, a nerve which is similar to the trigeminal nerve
Trigeminal nerve
The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...


Neuronal migration

Neuronal migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...

 is the method by which neurons travel from their origin or birth place to their final position in the brain. There are several ways they can do this, e.g. by radial migration or tangential migration. (see time lapse sequences of radial migration (also known as glial guidance) and somal translocation.)
Radial migration
Neuronal precursor cells proliferate in the ventricular zone of the developing neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...

. The first postmitotic
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 cells to migrate form the preplate which are destined to become Cajal-Retzius cells and subplate
The transient fetal subplate zone, together with the marginal zone and the cortical plate, represents the developmental anlage of the mammalian cerebral cortex...

 neurons. These cells do so by somal translocation. Neurons migrating with this mode of locomotion are bipolar and attach the leading edge of the process to the pia
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....

. The soma
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...

 is then transported to the pial surface by nucleokinesis, a process by which a microtubule "cage" around the nucleus elongates and contracts in association with the centrosome
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...

 to guide the nucleus to its final destination. Radial glia, whose fibers serve as a scaffolding for migrating cells, can itself divide or translocate to the cortical plate and differentiate either into astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...

s or neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s. Somal translocation can occur at any time during development.

Subsequent waves of neurons split the preplate by migrating along radial glia
Radial glia
Radial glial cells are a pivotal cell type in the developing central nervous system involved in key developmental processes, from patterning and neuronal migration to their recently discovered role as precursors during neurogenesis. They arise early in development from neuroepithelial cells...

l fibres to form the cortical plate. Each wave of migrating cells travel past their predecessors forming layers in an inside-out manner, meaning that the youngest neurons are the closest to the surface. It is estimated that glial guided migration represents 90% of migrating neurons in human and about 75% in rodents.

Tangential migration
Most interneurons migrate tangentially through multiple modes of migration to reach their appropriate location in the cortex. An example of tangential migration is the movement of interneurons from the ganglionic eminence
Ganglionic eminence
In neuroanatomy and neuroembryology, a ganglionic eminence is a transitory brain structure present in the embryonic and fetal stages of brain development. The eminences are found in the ventral part of the telencephalon, where they form bulges in the ventricles. These bulges develop into the basal...

 to the cerebral cortex. One example of ongoing tangential migration in a mature organism, observed in some animals, is the rostral migratory stream
Rostral migratory stream
The rostral migratory stream is a pathway found in the brain of some animals along which neuronal precursors that originated in the subventricular zone of the brain migrate to reach the main olfactory bulb . This pathway has been studied in the rodent, rabbit, and both the squirrel and rheusus...

 connecting subventricular zone
Subventricular 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....

 and olfactory bulb
Olfactory bulb
The olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...


Others modes of migration
There is also a method of neuronal migration called multipolar migration. This is seen in multipolar cells, which are abundantly present in the cortical intermediate zone. They do not resemble the cells migrating by locomotion or somal translocation. Instead these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers.

Neurotrophic factors

The survival of neurons is regulated by survival factors, called trophic factors. The neurotrophic hypothesis was formulated by Victor Hamburger and Rita Levi Montalcini based on studies of the developing nervous system. Victor Hamburger discovered that implanting an extra limb in the developing chick led to an increase in the number of spinal motor neurons. Initially he thought that the extra limb was inducing proliferation of motor neurons, but he and his colleagues later showed that there was a great deal of motor neuron death during normal development, and the extra limb prevented this cell death. According to the neurotrophic hypothesis, growing axons compete for limiting amounts of target-derived trophic factors and axons that neurons that fail to receive insufficient trophic support die by apoptosis. It is now clear that factors produced by a number of sources contribute to neuronal survival.

Nerve Growth Factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...

 (NGF): Rita Levi Montalcini and Stanley Cohen purified the first trophic factor, Nerve Growth Factor (NGF), for which they received the Nobel Prize. There are three NGF-related trophic factors: BDNF, NT3, and NT4, which regulate survival of various neuronal populations. The Trk proteins act as receptors for NGF and related factors. Trk is a receptor tyrosine kinase. Trk dimerization and phosphorylation leads to activation of various intracellular signaling pathways including the MAP kinase, Akt, and PKC pathways.

CNTF: Ciliary neurotrophic factor is another protein that acts as a survival factor for motor neurons. CNTF acts via a receptor complex that includes CNTFRα, GP130, and LIFRβ. Activation of the receptor leads to phosphorylation and recruitment of the JAK kinase, which in turn phosphorylates LIFRβ. LIFRβ acts as a docking site for the STAT transcription factors. JAK kinase phosphorylates STAT proteins, which dissociate from the receptor and translocate to the nucleus to regulate gene expression.

GDNF: Glial derived neurotrophic factor is a member of the TGFb family of proteins, and is a potent trophic factor for striatal neurons. The functional receptor is a heterodimer, composed of type 1 and type 2 receptors. Activation of the type 1 receptor leads to phosphorylation of Smad proteins, which translocate to the nucleus to activate gene expression.

Synapse formation

Neuromuscular junction
Much of our understanding of synapse formation comes from studies at the neuromuscular junction. The transmitter at this synapse is acetylcholine. The acetylcholine receptor (AchR) is present at the surface of muscle cells before synapse formation. The arrival of the nerve induces clustering of the receptors at the synapse. McMahan and Sanes showed that the synaptogenic signal is concentrated at 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....

. They also showed that the synaptogenic signal is produced by the nerve, and they identified the factor as Agrin
Agrin is a large proteoglycan whose best characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN...

. Agrin induces clustering of AchRs on the muscle surface and synapse formation is disrupted in agrin knockout mice. Agrin transuces the signal via MuSK receptor to rapsyn. Fischbach and colleagues showed that receptor subunits are selectively transcribed from nuclei next to the synaptic site. This is mediated by neuregulins.

In the mature synapse each muscle fiber is innervated by one motor neuron. However, during development many of the fibers are innervated by multiple axons. Lichtman and colleagues have studied the process of synapses elimination. This is an activity-dependent event. Partial blockage of the receptor leads to retraction of corresponding presynaptic terminals.

CNS synapses
Agrin appears not to be a central mediator of CNS synapse formation and there is active interest in identifying signals that mediate CNS synaptogenesis. Neurons in culture develop synapses that are similar to those that form in vivo, suggesting that synaptogenic signals can function properly in vitro. CNS synaptogenesis studies have focused mainly on glutamatergic synapses. Imaging experiments show that dendrites are highly dynamic during development and often initiate contact with axons. This is followed by recruitment of postsynaptic proteins to the site of contact. Stephen Smith and colleagues have shown that contact initiated by dendritic filopodia can develop into synapses.

Induction of synapse formation by glial factors: Barres and colleagues made the observation that factors in glial conditioned media induce synapse formation in retinal ganglion cell cultures. Synapse formation in the CNS is correlated with astrocyte differentiation suggesting that astrocytes might provide a synaptogenic factor. The identity of the astrocytic factors is not yet known.

Neuroligins and SynCAM as synaptogenic signals: Sudhof, Serafini, Scheiffele and colleagues have shown that neuroligins and SynCAM can act as factors that will induce presynaptic differentiation. Neuroligins are concentrated at the postsynaptic site and act via neurexins concentrated in the presynaptic axons. SynCAM is a cell adhesion molecule that is present in both pre- and post-synaptic membranes.

Synapse elimination

Several motorneurones compete for each neuromuscular junction, but only one survives till adulthood. Competition in vitro has been shown to involve a limited neurotrophic substance that is released, or that neural activity infers advantage to strong post-synaptic connections by giving resistance to a toxin also released upon nerve stimulation. In vivo it is suggested that muscle fibres select the strongest neuron through a retrograde signal.

See also

  • Neural development in humans
    Neural development in humans
    The study of neural development draws on both neuroscience and developmental biology to describe the cellular and molecular mechanisms by which complex nervous systems emerge during embryonic development and throughout life....

  • Axon guidance
    Axon guidance
    Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...

  • Pioneer neuron
    Pioneer neuron
    Pioneer neuron is a cell that is a derivative of preplate in the early stages of corticogenesis of the brain. Pioneer neurons settle in the marginal zone of the cortex and project to sub-cortical levels. In the rat, pioneer neurons are only present in prenatal brains...

  • Neural Darwinism
    Neural Darwinism
    Neural Darwinism, a large scale theory of brain function by Gerald Edelman, was initially published in 1978, in a book called The Mindful Brain...

  • Neurodevelopmental disorder
  • Pre- and perinatal psychology
    Pre- and perinatal psychology
    Prenatal and perinatal psychology is an interdisciplinary study of the foundations of health in body, mind, emotions and in enduring response patterns to life...

  • Brain development timelines
    Brain development timelines
    These are timelines of brain development events in different species.*Mouse brain development timeline*Macaque brain development timeline*Human brain development timeline-External links:* ...

  • Malleable intelligence
    Malleable intelligence
    Malleability of intelligence describes the processes by which human intelligence may be augmented through changes in neuroplasticity. These changes may come as a result of genetics, pharmacological factors, psychological factors, behavior, or environmental conditions...

  • Human brain development timeline
    Human brain development timeline
    Species: Homo SapiensFamily: Hominidae Order: PrimatesGestation: 270 days-External links:* — a website providing translation of brain developmental times among different species...

  • Mouse brain development timeline
    Mouse brain development timeline
    Species: Mus musculusFamily: Muridae Order: RodentiaGestation: 21 days Day Event Reference 9 cranial motor nuclei - peak of neurogenesis Finlay and Darlington 10 subplate -start of neurogenesis...

  • Macaque brain development timeline
    Macaque brain development timeline
    Species: Macaca mulattaFamily: Cercopithecidae Order: PrimatesGestation: 165 daysDates in days Day Event Reference 30 retinal ganglion cell generation - start of neurogenesis Robinson and Dreher 30...

External links

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