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在上皮形态发生过程中，单腔形成和HGF介导的细胞突起需要P-钙黏蛋白依赖性黏附。

P-cadherin-dependent adhesions are required for single lumen formation and HGF-mediated cell protrusions during epithelial morphogenesis.

作者信息

Tran Sydnie K, Lichtenberg Jessanne Y, Leonard Corinne E, Williamson Jessica R, Sterling Hazel R, Panek Grace K, Pearson Amanda H, Lopez Santiago, Lemmon Christopher A, Conway Daniel E, Hwang Priscilla Y

机构信息

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23220, USA.

Department of Mechanical Engineering, Iowa State University, Ames, IA 50011, USA.

出版信息

iScience. 2025 Jan 20;28(2):111844. doi: 10.1016/j.isci.2025.111844. eCollection 2025 Feb 21.

DOI:10.1016/j.isci.2025.111844

PMID:39981519

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11840494/

Abstract

During epithelial morphogenesis, , epithelial cells form cysts enclosing a single, hollow lumen and extend protrusions as a precursor for tubulogenesis Cell-cell adhesions (e.g., cadherins) contribute to successful execution of these processes; while there are many different cadherins, one less studied cadherin in epithelial morphogenesis is P-cadherin (CDH3). Here, we investigated the role of CDH3 on successful lumen formation and cell protrusions, using three-dimensional cultures of Madin-Darby canine kidney (MDCK) and CDH3 knockout cell lines. We show that depletion of CDH3 leads to perturbations of hollow lumen formation associated with defects in cell protrusions and tubulogenesis, mediated by Rho/ROCK pathway. CDH3 knockout cells exert lower forces on the surrounding environment compared to wild-type cells, suggesting CDH3 acts as a mechanosensor for stable cell protrusion establishment. Together, our data suggest that CDH3 has an essential function during epithelial morphogenesis by contributing to lumen formation and cell protrusions.

摘要

在上皮形态发生过程中，上皮细胞形成包绕单个中空管腔的囊肿，并延伸出突起作为肾小管发生的前体。细胞间黏附（如钙黏蛋白）有助于这些过程的成功执行；虽然有许多不同的钙黏蛋白，但在上皮形态发生中研究较少的一种钙黏蛋白是P-钙黏蛋白（CDH3）。在这里，我们使用麦迪逊-达比犬肾（MDCK）和CDH3基因敲除细胞系的三维培养物，研究了CDH3在成功形成管腔和细胞突起中的作用。我们发现，CDH3的缺失会导致中空管腔形成的扰动，这与细胞突起和肾小管发生缺陷有关，由Rho/ROCK信号通路介导。与野生型细胞相比，CDH3基因敲除细胞对周围环境施加的力更低，这表明CDH3作为一种机械传感器，有助于稳定细胞突起的形成。总之，我们的数据表明，CDH3在上皮形态发生过程中通过促进管腔形成和细胞突起发挥重要作用。