REGULATION OF NORMAL PROLIFERATION IN THE DEVELOPING CEREBRUM POTENTIAL ACTIONS OF TROPHIC FACTORS

We review here a computational model of neocortical histogenesis based upon experiments in the developing cerebral wall of the mouse. Though based upon experiments in mouse, commonalities of developmental histo ry and structure of neocortex across mammalian species suggest that th e principles which support this model will be generally applicable to neocortical evolution and development across species, In its scope the model spans the successive histogenetic events: cell proliferation, c ell migration, and the positioning of cell somata in neocortical layer s following migration. Neurons are produced in a pseudostratified epit helium (PVE) which lines the ventricular cavities of the embryonic cer ebrum. The parameters which determine the rate and total number of neu rons produced in the PVE are (1) the size of the founder population, ( 2) the number of integer cell cycles executed by the founder populatio n and its progeny in the course of the neuronogenetic interval, (3) th e growth fraction, and (4) the fraction of cells which exits the cycle (Q fraction) with each integer cycle. There is a systematic relations hip between the integer cycle of origin and the sequence of cell migra tion, position in the cortex, and the extent to which a set of postmig ratory neurons will be diluted in the cortex by the combined effects o f tissue growth and cell death. Variation across species in the number of integer cell cycles as a function of the rate of progression of Q may be expected to modulate profoundly the total numbers of neurons th at are produced but not the relative proportions of neurons assigned t o the major neocortical layers. (C) 1996 Academic Press, Inc.