SHARPS - MAMMALIAN ENHANCER-OF-SPLIT-RELATED AND HAIRY-RELATED PROTEINS COUPLED TO NEURONAL STIMULATION

In the mammalian central nervous system, a diverse group of basic heli x-loop-helix (bHLH) proteins is involved in the determination of proge nitor cells and, subsequently, in regulating neuronal differentiation. Here we report the identification of a novel subfamily of bHLH protei ns, defined by two mammalian enhancer-of-split- and hairy-related prot eins, termed SHARP-1 and SHARP-2. In contrast to known bHLH genes, det ectable transcription of SHARP genes begins at the end of embryonic de velopment marking differentiated neurons that have reached a final pos ition, and increases as postnatal development proceeds. in the adult, SHARP genes are expressed in subregions of the CNS that have been asso ciated with adult plasticity. In PC12 cells, a model system to study n eurite outgrowth, SHARP genes can be induced by NGF with the kinetics of an immediate-early gene. Similarly, within 1 h after the administra tion of kainic acid in vivo, SHARP-P is induced in neurons throughout the rat cerebral cortex. This suggests that neuronal bHLH proteins are also involved in the ''adaptive'' changes of mature CNS neurons which are coupled to glutamatergic stimulation.