Bron R, Vermeren M, Kokot N, Andrews W, Little GE, Mitchell KJ, Cohen J., Boundary cap cells constrain spinal motor neuron somal migration at motor exit points by a semaphorin-plexin mechanism, Neural Development, 30, 2, 2007, 21
Neural Development 30 2
Background: In developing neurons, somal migration and initiation of axon outgrowth often occur simultaneously and
are regulated in part by similar classes of molecules. When neurons reach their final destinations, however, somal
translocation and axon extension are uncoupled. Insights into the mechanisms underlying this process of disengagement
came from our study of the behaviour of embryonic spinal motor neurons following ablation of boundary cap cells. These
are neural crest derivatives that transiently reside at motor exit points, central nervous system (CNS):peripheral nervous
system (PNS) interfaces where motor axons leave the CNS. In the absence of boundary cap cells, motor neuron cell
bodies migrate along their axons into the periphery, suggesting that repellent signals from boundary cap cells regulate
the selective gating of somal migration and axon outgrowth at the motor exit point. Here we used RNA interference in
the chick embryo together with analysis of null mutant mice to identify possible boundary cap cell ligands, their receptors
on motor neurons and cytoplasmic signalling molecules that control this process.
Results: 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.
Conclusion: 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.
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