Open AccessRPM-1 AND DLK-1 regulate pioneer axon outgrowth by controlling Wnt signaling
Author(s) -
Eun Chan Park,
Christopher Rongo
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.164897
Subject(s) - biology , wnt signaling pathway , axon , axon guidance , neuroscience , ubiquitin ligase , nervous system , signal transduction , microbiology and biotechnology , ventral nerve cord , crosstalk , neuron , anatomy , ubiquitin , genetics , physics , gene , optics
Axons must correctly reach their targets for proper nervous system function, although we do not fully understand the underlying mechanism, particularly for the first “pioneer” axons. In C. elegans, AVG is the first neuron to extend an axon along the ventral midline, and this pioneer axon facilitates the proper extension and guidance of follower axons that comprise the ventral nerve cord. Here, we show that the ubiquitin ligase RPM-1 prevents the overgrowth of the AVG axon by repressing the activity of the DLK-1/p38 MAPK pathway. Unlike in damaged neurons, where this pathway activates CEBP-1, we find that RPM-1 and the DLK-1 pathway instead regulate the response to extracellular Wnt cues in developing AVG axons. The Wnt LIN-44 promotes the posterior growth of the AVG axon. In the absence of RPM-1 activity, AVG becomes responsive to a different Wnt, EGL-20, through a mechanism that seems independent of canonical Fz-type receptors. Our results suggest that RPM-1 and the DLK-1 pathway regulate axon guidance and growth by preventing Wnt signaling crosstalk.