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

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. Following epithelial-mesenchymal transition, avian trunk neural crest cell polarity determines directional migration but how this is established is unclear. Here, the authors find that the RhoGAP, Deleted in liver cancer 1, is asymmetrically localized in the cytoplasm, governing neural crest migratory polarization.

在上皮 - 间充质转化之后，禽类躯干神经嵴细胞（NCC）极性的获得是定向分层和迁移的先决条件，而这反过来对周围神经系统的发育至关重要。然而，这种细胞极化是如何建立和调控的仍然未知。在此我们证明，通过在体内和体外使用RHOA生物传感器，NCC极化的起始伴随着细胞后部细胞质中高度活化的RHOA以及其在前缘的波动活性。这种不同的RHOA活性决定了极化的神经嵴细胞形态和运动性，并由细胞前部细胞质中不对称定位的肝癌缺失基因（DLC1）所调控的RhoGAP调节。重要的是，DLC1与NEDD9的关联对其不对称定位和不同的RHOA活性至关重要。此外，神经嵴细胞特异性因子SOX9和SOX10分别调节NEDD9和DLC1的表达。这些结果呈现了一个SOX9/SOX10 - NEDD9/DLC1 - RHOA调控轴来控制NCC迁移极化。 在上皮 - 间充质转化之后，禽类躯干神经嵴细胞极性决定定向迁移，但这种极性是如何建立的尚不清楚。在此，作者发现RhoGAP（肝癌缺失基因1）在细胞质中不对称定位，调控神经嵴迁移极化。