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First published online 15 August 2007
doi: 10.1242/dev.007112

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.007112v1 134/18/3251    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palaisa, K. A. Articles by Granato, M. Search for Related Content PubMed PubMed Citation Articles by Palaisa, K. A. Articles by Granato, M.

Analysis of zebrafish sidetracked mutants reveals a novel role for Plexin A3 in intraspinal motor axon guidance

University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, Philadelphia, PA 19104-6058, USA.

^* Author for correspondence (e-mail: granatom{at}mail.med.upenn.edu)

Accepted 10 July 2007

SUMMARY

One of the earliest guidance decisions for spinal cord motoneurons occurs when pools of motoneurons orient their growth cones towards a common, segmental exit point. In contrast to later events, remarkably little is known about the molecular mechanisms underlying intraspinal motor axon guidance. In zebrafish sidetracked (set) mutants, motor axons exit from the spinal cord at ectopic positions. By single-cell labeling and time-lapse analysis we show that motoneurons with cell bodies adjacent to the segmental exit point properly exit from the spinal cord, whereas those farther away display pathfinding errors. Misguided growth cones either orient away from the endogenous exit point, extend towards the endogenous exit point but bypass it or exit at non-segmental, ectopic locations. Furthermore, we show that sidetracked acts cell autonomously in motoneurons. Positional cloning reveals that sidetracked encodes Plexin A3, a semaphorin guidance receptor for repulsive guidance. Finally, we show that sidetracked (plexin A3) plays an additional role in motor axonal morphogenesis. Together, our data genetically identify the first guidance receptor required for intraspinal migration of pioneering motor axons and implicate the well-described semaphorin/plexin signaling pathway in this poorly understood process. We propose that axonal repulsion via Plexin A3 is a major driving force for intraspinal motor growth cone guidance.

Key words: Zebrafish, Growth cone, Axon, Guidance, Myotome, Plexin A3, Sidetracked, Spinal motoneuron

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