MOTOR AXON SUBPOPULATIONS RESPOND DIFFERENTIALLY TO THE CHEMOREPELLENTS NETRIN-1 AND SEMAPHORIN-D

During development, growing motor axons are excluded from the ventral midline of the neural tube by diffusible chemorepellents emanating fro m this region. Molecular candidates for this chemorepellent activity i nclude semaphorin D and netrin-1; the latter is known to repel trochle ar motor axons. Qualitatively or quantitatively different responses to these molecules might underlie the initial deflection from the midlin e and subsequent segregation of motor axon trajectories. To test this idea, we have cocultured cell aggregates secreting netrin-1 or semapho rin D at a distance from tissue explants containing different motor ne uron subpopulations, in collagen gels. Cranial motor axons that projec t dorsally in vivo such as those of the trigeminal, facial, and glosso pharyngeal nuclei were repelled by both netrin-1 and semaphorin D. By contrast, ventrally projecting spinal motor axons and abducens axons w ere not affected by netrin-1. Spinal and abducens motor neurons also r esponded to semaphorin D. The ventrally projecting axons of oculomotor neurons were not repelled by netrin-1 or semaphorin D. Differential r esponsiveness to netrin-1 and semaphorin D could thus contribute to th e generation of dorsal and ventral motor axon pathways during developm ent.