Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2

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Abstract

Commissural axons switch on responsiveness to Wnt attraction during midline crossing to turn anteriorly after exiting the floor plate. We report here Sonic Hedgehog (Shh) downregulates Shisa2, which inhibits glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior-posterior (A-P) axis. Loss of Shisa2 lead to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A-P axis when Wntless, essential for Wnt secretion, is conditionally knocked out in the floor plate. The regulatory link between Shh and PCP signaling may also occur in other developmental processes.

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Keisuke Onishi

Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jalla, United States

Competing interests
The authors declare that no competing interests exist.
Yimin Zou

Neurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, United States

For correspondence
yzou@ucsd.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1092-5547

Funding

NINDS (NS047484)

Yimin Zou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were conducted in accordance with the NIH Guide for the Care and Use of LaboratoryAnimals and approved by the UCSD Animal Subjects Committee (Approved Protocol #: S06219, S06222).

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.