Some landmarks of embryonic neural development include the birth and differentiation of neurons from stem cell precursors, the migration of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axons from neurons and guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, and finally the lifelong changes 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, migration and axon guidance to their initial target areas. These processes are thought of as being independent of neural activity and sensory experience. Once axons reach their target areas, activity-dependent mechanisms come into play. Neural activity and sensory experience will mediate formation of new synapses, as well as synaptic plasticity, which will be responsible for refinement of the nascent neural circuits.
Developmental neuroscience uses a variety of animal models including mice Mus musculus , the fruit fly Drosophila melanogaster , the zebrafish Danio rerio, Xenopus laevis tadpoles and the worm Caenorhabditis elegans, among others.
After gastrulation the notochord—a flexible, rod-shaped body that runs along the back of the embryo—has been formed from the mesoderm. The notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm. This results in a strip of neuronal stem cells that runs along the back of the fetus. This strip is called the neural plate, and is the origin of the entire nervous system.
The neural plate folds outwards during the third week of gestation to form the neural groove. Beginning in the future neck region, the neural folds of this groove close to create the neural tube. The anterior (front) part of the neural tube is called the basal plate; the posterior (rear) part is called the alar plate. 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.
Late in the fourth week, the superior part of the neural tube flexes at the level of the future midbrain—the mesencephalon. Above the mesencephalon is the prosencephalon (future forebrain) and beneath it is the rhombencephalon (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) whilst its basal plate becomes the diencephalon. Finally, the optic vesicle grows to form an optic outgrowth.
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 BMPs, which are blocked by the organiser. The organiser may produce molecules such as follistatin, noggin and chordin which inhibit BMPs.
The ventral neural tube is patterned by Shh from the notochord, which acts as the inducing tissue. The Shh inducer causes differentiation of the floor plate. Shh-null tissue fails to generate all cell types in the ventral tube, suggesting Shh is necessary for its induction. The hypothesised mechanism suggests that Shh binds patched, relieving patched inhibition of smoothend, leading to activation of gli transcription factors.
In this context Shh acts as a morphogen - it induces cell differentiation dependent on its concentration. At low concentrations it forms ventral interneurones, at higher concentrations it induced motor neurone development, and at highest concentrations it induces floor plate differentiation. Failure of Shh-modulated differentiation causes haloprosencephaly.
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 transcription factor levels.
The hindbrain, for example, is patterned by Hox genes, which are expressed in overlapping domains along the anteroposterior axis. The 5' genes in this cluster and expressed most posteriorly. Hoxb-1 is expressed in rhombomere 4 and gives rise to the facial nerve. Without this Hoxb-1 expression, a nerve which is similar to the trigeminal nerve arises.
Neuronal precursor cells proliferate in the ventricular zone of the developing neocortex. The first postmitotic cells to migrate form the preplate which are destined to become Cajal-Retzius cells and subplate neurons. These cells do so by somal translocation. Neurons migrating with this mode of locomotion are bipolar and attachs the leading edge of the process to the pia. The soma 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 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 astrocytes or neurons. Somal translocation can occur at any time during development.
Subsequent waves of neurons split the preplate by migrating along radial glial 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.
Denervation sensitivity shows how nerve activity causes a deregulation of muscarinic receptors at non-synpatic sites. When the nerve is cut, receptors become upregulated in areas other than the synpase. Acetylcholine is thought to cause this effect via influx of calcium.
Expression patterns of semaphorin7A and plexinC1 during rat neural development suggest roles in axon guidance and neuronal migration.(Research article)(Report)
Aug 29, 2007; Authors: R Jeroen Pasterkamp (corresponding author) [1,2]; Sharon M Kolk ; Anita JCGM Hellemons ; Alex L Kolodkin...