REGULATION OF THE POU DOMAIN GENE SCIP DURING CEREBRAL CORTICAL DEVELOPMENT

The mammalian cerebral cortex is patterned into layers of neurons that share characteristic morphologies, physiological properties, and axon al connections. Neurons in the various layers are thought to acquire t heir lamina-specific identities shortly before the time of their final mitosis in the cortical ventricular zone. In order to investigate the molecular basis of laminar patterning in the CNS, we have performed i n situ hybridization studies of the POU homeodomain gene SCIP (also kn own as Tst-1 or Oct-6), which is expressed in proliferating Schwann ce lls in the PNS and O2A progenitor cells in the developing CNS. In the CNS of adult rats, SCIP is expressed at high levels in the cerebral co rtex, specifically in layer 5 pyramidal neurons that form subcortical axonal connections. SCIP is both temporally and spatially regulated du ring cortical development. Its initial expression in the intermediate zone and cortical plate is correlated with the early migration and dif ferentiation of layer 5 neurons. SCIP hybridization was not, however, observed within the ventricular zone during the period of neurogenesis . SCIP is also expressed at high levels in the neurons of cortical lay er 2/3, during their migration and differentiation within the cortical plate. This expression in the upper layers is apparently downregulate d during postnatal periods, with the adult pattern apparent by postnat al day 30 (P30). POU domain genes are thought to play a role in cell l ineage and cell fate decisions in several systems; thus, SCIP may serv e a function in generating discrete laminar phenotypes in the developi ng cerebral cortex. In addition, since SCIP is a putative repressor of myelin gene expression, our results suggest that SCIP plays a role in regulating transcription in differentiated CNS neurons as well as in proliferating glial precursors.