The neurodevelopmental processes that contribute to brain and CNS formation 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.
Neurulation is the formation of the neural tube from the ectoderm of the embryo. It follows gastrulation in all vertebrates. During gastrulation cells migrate to the interior of embryo, forming three germ layers— the endoderm (the deepest layer), mesoderm, and ectoderm (the surface layer)—from which all tissues and organs will arise. In a simplified way, it can be said that the ectoderm gives rise to skin and nervous system, the endoderm to the guts and the mesoderm to the rest of the organs.
After gastrulation, the notochord—a flexible, rod-shaped body that runs along the back of the embryo—has been formed from the mesoderm. During the third week of gestation, 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 to form the neural groove. Beginning in the future neck region, the neural folds of this groove close to create the neural tube Figure 2 (this form of neurulation is called primary neurulation). 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 Figure 1. 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.
In the fifth week, the alar plate of the prosencephalon expands to form the cerebral hemispheres (the telencephalon). The basal plate becomes the diencephalon. The diencephalon, mesencephalon, and rhombencephalon constitute the brain stem of the embryo. It continues to flex at the mesencephalon. The rhombencephalon folds posteriorly, which causes its alar plate to flare and form the fourth ventricle of the brain. The pons and the cerebellum form in the upper part of the rhombencephalon, while the medulla oblongata forms in the lower part.
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 attach the leading edge of the process to the pia. The soma is then transported to the pial surface by nucleokenisis, 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 fibers (also known as radial glia) can translocate to the cortical plate and differentiate either into astrocytes or neurons.
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 Cajal-Retzius cells from the cortical hem to the superfitial part of cortical neuroepithelium.
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 are molecules that promote and regulate neuronal survival in the developing nervous system. They are distinguished from ubiquitous metabolites necessary for cellular maintenance and growth by their specificity; each neurotrophic factor promotes the survival of only certain kinds of neurons during a particular stage of their development. In addition, it had been argued that neurotrophic factors are involved in many other aspects of neuronal development ranging from axonal guidance to regulation of neurotransmitter synthesis.