Normal development of the CNS
Normal development of the central nervous system:
2 weeks: the three primary layers of ectoderm, mesoderm, and endoderm form, and the notocord, a dorsal column of mesoderm, induces a plate of ectoderm above it to develop into the dorsal neural plate.
2–4 weeks: the neural plate forms a groove which develops into the neural tube which closes anteriorly at day 24 and posteriorly at day 29. Defects at this stage cause the dysraphic states, which range from anencephaly to spina bifida. Anteriorly the forebrain (prosencephalon) midbrain (mesencephalon), and hindbrain (rhombencephalon) develop from the second week with the rest of the neural plate forming the spinal cord. A secondary group of cells forms lateral to the neural tube, the neural crest, which provides a stream of elements of the peripheral nervous system and non-neural elements, e.g. melanocytes and parts of the face.
5–6 weeks: the main division of the forebrain into the primary elements of the cerebrum, basal ganglia, and diencephalon. The holoprosencephaly sequences occur at this stage.
8–16 weeks: cellular proliferation and the beginnings of differentiation of neuroblasts and glioblasts from the ventricular surface. Neuroblasts migrate radially along a glial fibrillary framework. This is followed by the formation of a primordial plexiform layer, or preplate, which forms a framework for the migration of nerves to the final six layers of the mature cerebral cortex. The superficial layers migrate late and the deep layers, e.g. pyramidal cells of layers V and VI, early.
This process is largely completed by 20 weeks, although some migration in the cerebellum and hippocampus continues well beyond this time, albeit at a slow rate. During this phase up to half of the cells formed die in an apparently programmed fashion known as apoptosis. During this phase microcephaly and the migrational disorders of the cortex and agenesis of the corpus callosum occur, with more minor cortical dysplasias occurring after 24 weeks, when gyri, and secondary and tertiary sulci appear.
The processes of dendritic development and synaptogenesis continue until 3–4 years, with particularly fast growth and pathway selection in the first year of extrauterine life. Myelination starts at 30 weeks in utero but is mainly extrauterine. Infantile hydrocephalus, syringomyelia, and associated conditions are considered elsewhere, and developmental anomalies of the skull and skeleton, such as the craniosynostoses, may also affect the central nervous system. Mentioned below are some of the more common congenital malformations of the brain.
The genetic factors influencing normal and deviant central nervous system development have been the subject of a great deal of research, with a number of mouse models providing close analogies to human diseases. The identification of chromosome and single-gene defects with predominant effects upon the CNS has increased, and approximately one-third of the human genome has effects upon the nervous system, particularly timed developmental effects. Environmental influences, which include maternal illness and a large number of teratogens, have also been explored so that genetic risks and preventive measures can be defined more precisely (Harding and Copp 1997).
One group of disorders arises from abnormal morphogenesis, i.e. the major primary structural process of neuroblast migration and neurepithelial elaboration, including neural-tube defects and neuronal migration defects. A second group of disorders arises from defects in the regional specification of neurepithelium by organizing genes, particularly the HOX genes.
A third area of great interest in developmental neurobiology is the phenomena of programmed cell death, whereby large numbers of neuroblasts and neurons fail to survive development through a process of cell death quite distinct from necrosis, i.e. apoptosis. There is a great deal of interest in the interaction of environmental and genetic effects in the developing cortex. The classic model of lack of development of the visual cortex and amblyopia with congenital cataracts has prompted the search for other ‘amblyopias’ secondary to lack of stimulus and experience.
Origin: Brain's Diseases of the Nervous System