Molecular analysis of axon repulsion by the notochord

Christopher N.G. Anderson, Kunimasa Ohta, Marie M. Quick, Angeleen Fleming, Roger Keynes, David Tannahill

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Abstract

During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.

Original languageEnglish
Pages (from-to)1123-1133
Number of pages11
JournalDevelopment
Volume130
Issue number6
DOIs
Publication statusPublished - Mar 1 2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Anderson, C. N. G., Ohta, K., Quick, M. M., Fleming, A., Keynes, R., & Tannahill, D. (2003). Molecular analysis of axon repulsion by the notochord. Development, 130(6), 1123-1133. https://doi.org/10.1242/dev.00327