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 and Martin Cheung ()
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Jessica Aijia Liu: The University of Hong Kong
Yanxia Rao: The University of Hong Kong
May Pui Lai Cheung: The University of Hong Kong
Man-Ning Hui: The University of Hong Kong
Ming-Hoi Wu: The University of Hong Kong
Lo-Kong Chan: The University of Hong Kong
Irene Oi-Lin Ng: The University of Hong Kong
Ben Niu: The University of Hong Kong
Kathryn S. E. Cheah: The University of Hong Kong
Rakesh Sharma: The University of Hong Kong
Louis Hodgson: Albert Einstein College of Medicine
Martin Cheung: The University of Hong Kong

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01107-0

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