A DEVELOPMENTAL-STUDY OF CYCLIC AMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB) BY IN-SITU HYBRIDIZATION HISTOCHEMISTRY AND IMMUNOCYTOCHEMISTRYIN THE RAT NEOCORTEX

Cyclic AMP (cAMP) mediates the hormonal stimulation of a number of euk aryotic genes by directing the protein kinase A (PK-A)-dependent phosp horylation of the transcription factor CREB. Somatostatin is one such gene known to be transcriptionally activated by cAMP via CREB. In view of the role somatostatin plays in the regulation of neocortical devel opment, we examined the early expression of CREB mRNA and protein (fro m E10 to E14) in the rat neocortex by in situ hybridization and immuno cytochemistry. mRNA for CREB was detected in all layers of the develop ing neocortex from E10 to E14. CREB immunoreactivity (CREB IR) was als o observed in most cortical cells by E10. However, the number of CREB- immunoreactive nuclei decreased thereafter, and on E14 there were immu noreactive cells only in the preplate. A moderate amount of somatostat in mRNA was observed on E16 in layer I, which is produced from the pre plate. This stage specific expression of the CREB protein in the devel oping neuroepithelium suggests that by regulating transcription of som e peptides including somatostatin, CREB plays a role in cortical devel opment,