The wonder of development is that a structure as complex as the human brain originates from a flat sheet of embryologic ectoderm. The final, formed brain shows remarkable order in its predictable cortical layering, its diversity of cortical areas, and the numerous networks linking specific cortical areas and subcortical structures. To have cells choosing to become a certain neuronal type, attaining the correct laminar position, finding the correct target, and expressing the correct neurotransmitters at first seems overwhelmingly difficult. However, the final, breathtakingly complex set of connections in the human brain depends on a series of much simpler decisions as neurons become progressively more restricted in the choices they make. These decisions require the subtle interplay of genetic and environmental factors; much has been learned at a molecular level about these processes. At first glance this information seems most relevant to mental retardation or autistic disorder, in which abnormal brain development results in lifelong disability. However, even schizophrenia is believed to originate in subtle aberrant brain development, and understanding it requires an understanding of its etiology.
[...] Aberrations in the formation of neural ectoderm or in the formation of neuroblasts are likely to result in gross abnormalities like anencephaly. A generalized failure of the migration of daughter neurons into cortical layers is seen in a lissencephalic brain, characterized by an agyric (smooth) cerebral surface. Mutations in certain cell adhesion molecules affect neural migration or axonal outgrowth, and are associated with inherited hydrocephalus. Such gross pathology is unlikely to result in an illness appreciated as psychiatric because children with these disorders have severe mental retardation and neurological syndromes. [...]
[...] Neuronal Migration Once neurons are born in the ventricular zone, they migrate past earlier born neurons to assume their final laminar position. The formation of the six cortical layers is complete between gestational age 26 and 29 weeks. To reach their laminar location, neurons migrate along radial glial fibers that stretch from the ventricular to superficial surface, a journey that may take place over tens of millimeters. Neurons must travel through a complex, rapidly expanding zone containing afferents from the thalamus and other cortical areas. [...]
[...] Molecules crucial to normal brain development and postnatal plasticity are being investigated in schizophrenia. In brains of persons with schizophrenia abnormalities of NCAM have been reported. GAP-43 is essential for the initial establishment and reorganization of synaptic connections, and remains high throughout life in the limbic system and neocortex, areas involved in the processing and storage of information. In frontal cortex and visual association areas of persons with schizophrenia, levels of GAP- 43 protein are increased, which is perhaps a reflection of the plasticity of inputs to prefrontal cortex. [...]
[...] neural plate, invaginates to form the neural tube as cells are progressively determined to form forebrain, midbrain, and hindbrain even before any neurons have been generated. On the inner surface of the neural tube there is a rapidly dividing pseudostratified epithelium that forms a ventricular zone. From the neural ectoderm arise neuroblasts, which are precursor cells located in the ventricular zone. Neuroblasts divide and produce a lineage of daughter cells that migrate into the developing cortex to form cortical neurons. [...]
[...] This suggests that the molecule is crucial for the development of neural circuits controlling a subset of behavior. There are mutant mice strains characterized by abnormal neural migration localized to the hippocampus. The hippocampus is divided into areas such as CA1, CA2, and CA3. The neurons of the hippocampus are generated during characteristic prenatal intervals in the ventricular zone lining the lateral ventricle. As in other cortical areas, the neurons migrate along primarily radial glial fibers to reach their final location. [...]
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