神经嵴细胞是从神经上皮脱落的多潜能细胞，迁移于胚胎全身。异常的迁移导致发育缺陷。动物模型正在促进我们对神经嵴异常的理解，但现实中的迁移行为却知之甚少。在这里，我们证明小鼠神经嵴细胞在体内表现出基于肌动蛋白的膜足和须足。通过使用神经嵴特异性基因敲除或抑制剂，我们表明丝氨酸/苏氨酸激酶糖原合成酶激酶-3 (GSK3)和细胞骨架调节因子膜足素 (Lpd) 在膜足形成中起到关键作用，同时抑制了焦点粘附的成熟。Lpd是GSK3的底物，Lpd的磷酸化有利于与Scar/WAVE复合物 (膜足形成) 作用，而减少与VASP和Mena的相互作用 (粘附成熟和须足形成)。这对哺乳动物神经嵴迁移中细胞骨架调控的理解对神经嵴异常和癌症具有普遍意义。版权所有 ©2023作者。由Elsevier Inc.发表，保留所有权利。

Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating throughout the embryo. Aberrant migration causes developmental defects. Animal models are improving our understanding of neural crest anomalies, but in vivo migration behaviors are poorly understood. Here, we demonstrate that murine neural crest cells display actin-based lamellipodia and filopodia in vivo. Using neural crest-specific knockouts or inhibitors, we show that the serine-threonine kinase glycogen synthase kinase-3 (GSK3) and the cytoskeletal regulator lamellipodin (Lpd) are required for lamellipodia formation while preventing focal adhesion maturation. Lpd is a substrate of GSK3, and phosphorylation of Lpd favors interactions with the Scar/WAVE complex (lamellipodia formation) at the expense of VASP and Mena interactions (adhesion maturation and filopodia formation). This improved understanding of cytoskeletal regulation in mammalian neural crest migration has general implications for neural crest anomalies and cancer.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.