Cellular aspects of brain development.

The formation of the central nervous system begins early in development with the induction of the neural ectoderm on the dorsal surface of the embryo. Subsequently, the neural ectoderm plate changes its shape to form a neural groove and eventually, a neural tube. The wall of the neural tube is composed of germinal cells, collectively called the neuroepithelium, that produces neurons and glia throughout the central nervous system (CNS). Three points will be made about cellular production in the CNS: (1) The neuroepithelium forms expansions (brain vesicles), folds, and lobules characteristic of particular CNS regions. The hypothesis that neuroepithelial "anatomy" is a blueprint for proper anatomical development of the CNS will be discussed. (2) Using tritiated thymidine autoradiography in the developing rat, we have found that the neuroepithelium generates neuronal populations according to specific timetables during CNS organogenesis. Some populations are produced early in a 1-2 day period, others are produced later during a 5-7 day period, while still others are produced after birth for periods of a few weeks. (3) By exposing perinatal rat pups to low level X-irradiation, we find that killing neuronal precursors and young postmitotic neurons results in permanent reductions in the number of cells that constitute the targeted neuronal populations. Even though some development continues after the X-ray exposures, there is no compensatory increase in cell proliferation to replace the lost cells. The implications of this finding will be discussed in light of the permanence of neurotoxic insults during human CNS development.