PACAP is an anti-mitogenic signal in developing cerebral cortex

In developing cerebral cortex, precise control of proliferation is required because the number of precursors determines the final number of neurons, regulating final size1. Although mitogens have been defined, their sustained expression throughout neurogenesis2,3,4 suggests that additional signals directly inhibit mitogenesis. Our findings of embryonic expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) ligand/receptor system and mitotic inhibition mediated by endogenous peptide and the cAMP pathway in vivo indicate that anti-mitogenic signals actively restrain growth factor-induced proliferation during development.