Neuropilin-2 Regulates the Development of Select Cranial and Sensory Nerves and Hippocampal Mossy Fiber Projections

coordinate action of attractive and repulsive mechanisms (Tessier-Lavigne and Goodman, 1996). One large family of secreted and transmembrane proteins that function in repulsion are the semaphorins, which are characterized by the presence of a conserved ‫005ف‬ brate semaphorins are those in class 3, with six known † Department of Neurology members (Sema3A–Sema3F). These semaphorins have University of California been shown to be chemorepulsive molecules, able to San Francisco, California 94243-0014 induce growth cone collapse when applied acutely and ‡ INSERM U106 uniformly and to steer axons away when presented as a Bâ timent de Pé diatrie point source; some secreted and transmembrane sema-Hô pital de la Salpé triè re phorins have also been reported to act as chemoattrac-47 Boulevard de I'Hô pital tants France The receptor mechanisms that mediate the repulsive § Department of Molecular and Cell Biology actions of class 3 semaphorins have been the subject University of California of intense study over the past several years. The evi-Berkeley, California 94720 dence to date indicates that individual class 3 semapho-Department of Integrative Biology rin receptors are complexes formed from members of University of Basel two transmembrane receptor families, neuropilins and Rheinsprung 9 plexins. Plexins appear to be receptors for several other CH-4051 Basel classes of semaphorins (classes 2, 4, and 7) in inverte-, apparently functioning directly to bind those semaphorins. In the case Summary of class 3 semaphorins, however, plexins appear to provide only a signaling moiety in a receptor complex (Taka-Neuropilin-1 and neuropilin-2 bind differentially to dif-hashi et al., 1999; Tamagnone et al., 1999), with ligand ferent class 3 semaphorins and are thought to provide binding mediated by members of the neuropilin family, the ligand-binding moieties in receptor complexes neuropilin-1 and-2 (Chen et al., 1997; He and Tessier-mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 The neuropilins are a small family of transmembrane through analysis of a neuropilin-2 mutant mouse, proteins implicated in a variety of biological functions which is viable and fertile. Repulsive responses of The first characterized defects are observed in the development of several member, neuropilin-1, was originally identified as a cell cranial nerves, in the initial central projections of spinal surface antigen expressed in the Xenopus laevis retino-sensory axons, and in the anterior commissure, habe-tectal system (Takagi et al., 1991). Neuropilin-1 homo-nulo-interpeduncular tract, and the projections of hip-logs were later isolated in chick (Takagi et al., 1995), pocampal …