Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Melissa Hernandez-Fleming, Ethan W. Rohrbach, Greg J. Bashaw
Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors.

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Teaser

In bilaterally symmetric animals, assembling precise neural circuits at the midline is critical for the coordination of the two sides of the body. Hernandez-Fleming et al. now uncover an important role for Sema-1a reverse signaling in controlling midline axon crossing.


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