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

Jessica Aijia Liu; Yanxia Rao; May Pui Lai Cheung; Man Ning Hui; Ming Hoi Wu; Lo Kong Chan; Irene Oi Lin Ng; Ben Niu; Kathryn S.E. Cheah; Rakesh Sharma; Louis Hodgson; Martin Cheung

doi:10.1038/s41467-017-01107-0

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

Jessica Aijia Liu, Yanxia Rao, May Pui Lai Cheung, Man Ning Hui, Ming Hoi Wu, Lo Kong Chan, Irene Oi Lin Ng, Ben Niu, Kathryn S.E. Cheah, Rakesh Sharma, Louis Hodgson, Martin Cheung

Molecular Pharmacology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	1185
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01107-0
State	Published - Dec 1 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-017-01107-0

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title = "Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration",

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.",

author = "Liu, {Jessica Aijia} and Yanxia Rao and Cheung, {May Pui Lai} and Hui, {Man Ning} and Wu, {Ming Hoi} and Chan, {Lo Kong} and Ng, {Irene Oi Lin} and Ben Niu and Cheah, {Kathryn S.E.} and Rakesh Sharma and Louis Hodgson and Martin Cheung",

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doi = "10.1038/s41467-017-01107-0",

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AU - Liu, Jessica Aijia

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AU - Hui, Man Ning

AU - Wu, Ming Hoi

AU - Chan, Lo Kong

AU - Ng, Irene Oi Lin

AU - Niu, Ben

AU - Cheah, Kathryn S.E.

AU - Sharma, Rakesh

AU - Hodgson, Louis

AU - Cheung, Martin

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

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

Abstract

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