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DLC1 的不对称定位为鸟类躯干神经嵴的定向分层和迁移定义了极性。

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

机构信息

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Nat Commun. 2017 Oct 30;8(1):1185. doi: 10.1038/s41467-017-01107-0.

DOI:10.1038/s41467-017-01107-0
PMID:29084958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5662599/
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.

摘要

在发生上皮-间充质转化后，禽类干骺端神经嵴细胞（NCC）获得极性是定向脱层和迁移的前提，而这反过来又是周围神经系统发育所必需的。然而，这种细胞极化是如何建立和调节的仍然未知。在这里，我们证明，使用体内和体外的 RHOA 生物传感器，NCC 极化的开始伴随着细胞质中细胞后部高度激活的 RHOA 及其在前缘的波动活性。这种差异 RHOA 活性决定了极化的 NC 形态和运动性，并受细胞质中不对称定位的肝肿瘤缺失 RhoGAP (DLC1) 的调节。重要的是，DLC1 与 NEDD9 的结合对于其不对称定位和差异 RHOA 活性至关重要。此外，NC 决定因子 SOX9 和 SOX10 分别调节 NEDD9 和 DLC1 的表达。这些结果提出了一个 SOX9/SOX10-NEDD9/DLC1-RHOA 调控轴来控制 NCC 的迁移极化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/f8d3d22f47f8/41467_2017_1107_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/1c36b770e694/41467_2017_1107_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/1b694a651fb4/41467_2017_1107_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/abf97d045770/41467_2017_1107_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/e9177c710a9a/41467_2017_1107_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/0324038c1760/41467_2017_1107_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/4564a5e01e8e/41467_2017_1107_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/d9f947215976/41467_2017_1107_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/f8d3d22f47f8/41467_2017_1107_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/1c36b770e694/41467_2017_1107_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/1b694a651fb4/41467_2017_1107_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/abf97d045770/41467_2017_1107_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/e9177c710a9a/41467_2017_1107_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/0324038c1760/41467_2017_1107_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/4564a5e01e8e/41467_2017_1107_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/d9f947215976/41467_2017_1107_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c8/5662599/f8d3d22f47f8/41467_2017_1107_Fig8_HTML.jpg

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