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In the homozygous (but not the heterozygous) reelermutant, disruption of neuron migration leads to a major perturbation of the cortical environment that in turn could modify (1) the specification of neuronal fate and (2) the proliferation dynamics of cortical precursors. To investigate these issues, tritiated thymidine 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 appropriate 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 postmigratory compartment. On the other hand, neither areal identity nor the chronology of production of layer-specific neuronal phenotype seems to depend on the integrity of the cellular environment.

Neurogenesis and Commitment of Corticospinal Neurons inreeler