Ectopic semaphorin-1a functions as an attractive guidance cue for developing peripheral neurons

Abstract

Transmembrane and secreted glycoproteins of the semaphorin family are typically classified as inhibitory neuronal guidance molecules. However, although chemorepulsive activity has been demonstrated for several semaphorin family members, little is known about the function of the numerous transmembrane semaphorins identified to date. Here we demonstrated that the extracellular semaphorin domain of a transmembrane semaphorin, semaphorin-1a, could actively perturb axon pathfinding in vivo when presented homogenously as a recombinant freely soluble factor. When ectopic overexpression was limited to defined epithelial regions, semaphorin-1a could directly steer axons by acting as an attractive guidance molecule.

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Figure 1: Recombinant Sema-1a construct.
Figure 2: Ectopic rSema-1a induces defects in Ti1-axon guidance.
Figure 3: Schematic summary of rSema-1a induced Ti1 axon pathfinding defects.
Figure 4: Dose–response curve comparing the activity of soluble, dimerized or clustered rSema-1a.
Figure 5: Full-length Sema-1a formed microscopically visible aggregates on the cell surface.
Figure 6: Ti1 growth cones turned toward ectopic S2 and COS cells expressing Sema-1a.

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Acknowledgements

We thank Edmond T. Wong for discussions and suggestions, David Bentley for reviewing the manuscript and Alex L. Kolodkin for supplying the full-length clone AK74. J.T.W. was supported by a Doctoral Studentship from the Rick Hansen Institute. The work was supported in part by grants from the Medical Research Council of Canada (MT-13246) and Natural Science and Engineering Research Council of Canada (OGP0171387; T.P.O.).

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Correspondence to Timothy P. O'Connor.

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Wong, J., Wong, S. & O'Connor, T. Ectopic semaphorin-1a functions as an attractive guidance cue for developing peripheral neurons. Nat Neurosci 2, 798–803 (1999). https://doi.org/10.1038/12168

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