Cerebral cortical specification by early potential restriction of progenitor cells and later phenotype control of postmitotic neurons

Neurons expressing latexin, a carboxypeptidase A inhibitor, are restricted to lateral areas in the cerebral cortex of adult and early postnatal rats. To address the precise timing of cortical regional specification at the cel lular level, we monitored latexin expression in developing cortical cells u nder specific conditions in vitro. Individual cortical cells were labeled w ith 5-bromo-2'-deoxyuridine in vivo, dissociated and exposed to a defined n ew environment in a monolayer or a reaggregated-cell culture system. While a substantial fraction of early progenitor cells derived from the lateral c erebral wall became latexin-expressing neurons in both systems, far fewer p rogenitors from dorsal cortex did so under the same environmental condition s, indicating early establishment of cortical regional specification at the progenitor cell level. Furthermore, it was shown that the probability for postmitotic cells within lateral cortex to become latexin-expressing neuron s was influenced by temporally regulated regional environmental signals. Th ese findings suggest that developing cortical cells are progressively speci fied for a regional molecular phenotype during both their proliferative and postmitotic periods.