Neurogenesis and commitment of corticospinal neurons

In the homozygous (but not the heterozygous) reeler mutant, disruption of neuron migration leads to a major perturbation of the cortical environment that in turn could modify (1) the spec-ification of neuronal fate and (2) the proliferation dynamics of cortical precursors. To investigate these issues, tritiated thymi-dine injections during cortical neurogenesis were coupled with postnatal injections of a retrograde tracer in the spinal cord to accurately measure the neurogenesis of corticospinal neurons in the heterozygous and homozygous mutant. The homozygous reeler shows (1) strict conservation of area-specific timetables of corticospinal neuron generation; (2) neurons with the appro-priate birthdates show an enhanced probability of projecting to the spinal cord; (3) during early stages of corticogenesis, there is a reduced rate of neuron production followed at later stages by an increased rate of neuron production; and (4) these changes in the rate of neuron production were shown to be at least partially attributable to changes in the proportions of differentiative divisions. Taken together, our results show that in the developing cortex, the neurogenesis and specification of a given neuronal phenotype are partially controlled by the post-migratory compartment. On the other hand, neither areal iden-tity nor the chronology of production of layer-specific neuronal phenotype seems to depend on the integrity of the cellular environment. Key words: corticogenesis; mouse; somatosensory cortex; development; proliferation; tritiated thymidine Birthdating experiments coupled with manipulation of the cellu-lar environment of the cortex show that early-generated neuron