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The Ciliary Protein Arl13b Functions Outside of the Primary Cilium in Shh-Mediated Axon Guidance.

Abstract：

:The small GTPase Arl13b is enriched in primary cilia and regulates Sonic hedgehog (Shh) signaling. During neural development, Shh controls patterning and proliferation through a canonical, transcription-dependent pathway that requires the primary cilium. Additionally, Shh controls axon guidance through a non-canonical, transcription-independent pathway whose connection to the primary cilium is unknown. Here we show that inactivation of Arl13b results in defective commissural axon guidance in vivo. In vitro, we demonstrate that Arl13b functions autonomously in neurons for their Shh-dependent guidance response. We detect Arl13b protein in axons and growth cones, far from its well-established ciliary enrichment. To test whether Arl13b plays a non-ciliary function, we used an engineered, cilia-localization-deficient Arl13b variant and found that it was sufficient to mediate Shh axon guidance in vitro and in vivo. Together, these results indicate that, in addition to its ciliary role in canonical Shh signaling, Arl13b plays a cilia-independent role in Shh-mediated axon guidance.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ferent J,Constable S,Gigante ED,Yam PT,Mariani LE,Legué E,Liem KF Jr,Caspary T,Charron F

doi

10.1016/j.celrep.2019.11.015

subject

Has Abstract

pub_date

2019-12-10 00:00:00

pages

3356-3366.e3

issue

11

issn

2211-1247

pii

S2211-1247(19)31486-X

journal_volume

29

pub_type

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