%0 Journal Article
%T Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin-plexin mechanism
%A Romke Bron
%A Matthieu Vermeren
%A Natalie Kokot
%A William Andrews
%A Graham E Little
%A Kevin J Mitchell
%A James Cohen
%J Neural Development
%D 2007
%I BioMed Central
%R 10.1186/1749-8104-2-21
%X We demonstrate that targeted knock down in motor neurons of Neuropilin-2 (Npn-2), a high affinity receptor for class 3 semaphorins, causes their somata to migrate to ectopic positions in ventral nerve roots. This finding was corroborated in Npn-2 null mice, in which we identified motor neuron cell bodies in ectopic positions in the PNS. Our RNA interference studies further revealed a role for Plexin-A2, but not Plexin-A1 or Plexin-A4. We show that chick and mouse boundary cap cells express Sema3B and 3G, secreted semaphorins, and Sema6A, a transmembrane semaphorin. However, no increased numbers of ectopic motor neurons are found in Sema3B null mouse embryos. In contrast, Sema6A null mice display an ectopic motor neuron phenotype. Finally, knockdown of MICAL3, a downstream semaphorin/Plexin-A signalling molecule, in chick motor neurons led to their ectopic positioning in the PNS.We conclude that semaphorin-mediated repellent interactions between boundary cap cells and immature spinal motor neurons regulates somal positioning by countering the drag exerted on motor neuron cell bodies by their axons as they emerge from the CNS at motor exit points. Our data support a model in which BC cell semaphorins signal through Npn-2 and/or Plexin-A2 receptors on motor neurons via a cytoplasmic effector, MICAL3, to trigger cytoskeletal reorganisation. This leads to the disengagement of somal migration from axon extension and the confinement of motor neuron cell bodies to the spinal cord.The migration of neurons is a key process in the development of the nervous system since sites of neurogenesis are often separated by long distances from final destinations. Neuron migration is complex, requiring synchronisation of multiple stepwise processes that differ in important respects from other types of migrating cells. In non-neuronal cells, nucleokinesis or somal translocation is tightly coupled to that of the exploratory lamellopodia. Neuron migration, in contrast, is initiated independ
%U http://www.neuraldevelopment.com/content/2/1/21