Structure and expression of murine mgcRacGAP: its developmental regulationsuggests a role for the Rac/MgcRacGAP signalling pathway in neurogenesis

Rho-family GTPases regulate a wide range of biological functions including cell migration, cell adhesion and cell growth. Recently, results from studi es in vivo in Drosophila, mouse and humans have demonstrated the involvemen t of these GTPases in mechanisms controlling neuronal differentiation and t he development of the central nervous system (CNS). However, the signalling pathways underlying these functions and the proteins directly regulating R hoGTPases in developing neurons are poorly defined. Here we report the stru cture and expression pattern of the murine orthologue of mgcRacGAP, a human gene encoding a RacGTPase partner expressed in male germ cells [Toure, Dor seuil, Morin, Timmons, Jegou, Reibel and Gacon (1998) J. Biol. Chem. 273, 6 019-6023]. In contrast with that from humans, murine mgcRacGAP encodes two distinct transcripts. Both are developmentally regulated. A 2.2 kb transcri pt is strongly expressed in mature testis and is up-regulated with spermato genesis. A 3 kb RNA is predominant in the embryo and is expressed primarily in the CNS during the neurogenic phase, decreasing after birth. In situ hy bridization analysis in embryonic-day 14.5 mouse embryos demonstrates a pre ferential expression of mgcRacGAP in the proliferative ventricular zone of the cortex. In addition to the expression of mgcRacGAP in male germ cells a lready reported in humans and suggesting an involvement in spermatogenesis, we characterize an embryonic transcript whose expression is closely correl ated with neurogenesis. This result addresses the question of the role of R ac/MgcRacGAP pathway in neuronal proliferation.