Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration

Nature Communications
Jessica Aijia LiuMartin Cheung

Abstract

Following epithelial-mesenchymal transition, acquisition of avian trunk neural crest cell (NCC) polarity is prerequisite for directional delamination and migration, which in turn is essential for peripheral nervous system development. However, how this cell polarization is established and regulated remains unknown. Here we demonstrate that, using the RHOA biosensor in vivo and in vitro, the initiation of NCC polarization is accompanied by highly activated RHOA in the cytoplasm at the cell rear and its fluctuating activity at the front edge. This differential RHOA activity determines polarized NC morphology and motility, and is regulated by the asymmetrically localized RhoGAP Deleted in liver cancer (DLC1) in the cytoplasm at the cell front. Importantly, the association of DLC1 with NEDD9 is crucial for its asymmetric localization and differential RHOA activity. Moreover, NC specifiers, SOX9 and SOX10, regulate NEDD9 and DLC1 expression, respectively. These results present a SOX9/SOX10-NEDD9/DLC1-RHOA regulatory axis to govern NCC migratory polarization.

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Citations

Apr 21, 2018·Genesis : the Journal of Genetics and Development·Nadège GouignardEric Theveneau
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Jul 11, 2021·Cells & Development·Meritxell Font-NogueraMagali Suzanne

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Methods Mentioned

BETA
GTPases
GTPase
fluorescence
biosensor
delamination
FRET
fluorescence activated cell sorting
pull-down
FRET-biosensor
immunoprecipitation

Software Mentioned

Metamorph
Gene Tools
Ingenuity Pathway Knowledge base
Primer3Plus
ImageJ

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