Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT

The Journal of Cell Biology
Erica J Hutchins, Marianne E Bronner

Abstract

Neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) that proceeds head to tailward to exit from the neural tube. In this study, we show that the secreted molecule Draxin is expressed in a transient rostrocaudal wave that mirrors this emigration pattern, initiating after neural crest specification and being down-regulated just before delamination. Functional experiments reveal that Draxin regulates the timing of cranial neural crest EMT by transiently inhibiting canonical Wnt signaling. Ectopic maintenance of Draxin in the cranial neural tube blocks full EMT; while cells delaminate, they fail to become mesenchymal and migratory. Loss of Draxin results in premature delamination but also in failure to mesenchymalize. These results suggest that a pulse of intermediate Wnt signaling triggers EMT and is necessary for its completion. Taken together, these data show that transient secreted Draxin mediates proper levels of canonical Wnt signaling required to regulate the precise timing of initiation and completion of cranial neural crest EMT.

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Citations

Oct 2, 2019·Cells·Yu JiChengji J Zhou
Jan 23, 2020·Journal of Cell Science·Karyn Jourdeuil, Lisa A Taneyhill
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Feb 6, 2019·Developmental Biology·Kamil AhsanVictoria E Prince
Feb 23, 2021·Frontiers in Physiology·Erica J HutchinsMarianne E Bronner
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Jun 13, 2020·Current Opinion in Cell Biology·Michael L PiacentinoMarianne E Bronner

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Methods Mentioned

BETA
delamination
nuclear translocation
PCR
transfection
electrophoresis

Software Mentioned

Prism
ImageJ
Fiji
GraphPad
Adobe Photoshop
ZEISS
Gene Tools
Zen 2 Blue

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