Mechanisms of junctional actin organization in epidermal morphogenesis and homeostasis

连接肌动蛋白组织在表皮形态发生和稳态中的机制

• 批准号: 273724076
• 负责人: Professorin Dr. Carien Niessen, Ph.D.
• 金额: --
• 依托单位: Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/273724076?language=en
• 关键词: Mechanisms; junctional; actin; organization; epidermal

The skin epidermis is a self-renewing stratifying epithelium and crucial for skin barrier function. Basal epidermal stem cells balance selfrenewal with a spatiotemporal controlled differentiation program of their progeny that is accompanied by spatial coordinated cell shape changes. However, whether these shape changes control positioning and cell fate is not clear. The classical cadherins couple intercellular adhesion to the force generating actomyosin cytoskeleton in specialized adherens junctions (AJs). These junctions thus allow cells to communicate forces across cells to coordinate cell shape changes and cellular responses. In the previous period of this SPP we identified E-cadherin in AJs as a force sensing and transducing protein that coordinates signaling and mechanical responses to regulate initial epidermal differentiation steps as well as final barrier formation. E-cadherin does so by tissue polarization of different AJ mechanical states and differential cortical actin network organization. The overall goal of the next SPP period is to determine how AJs control different states of F-actin organization and ask whether and how these states integrate cell position with cell fate and function. Together, the experiments proposed will likely contribute to a better understanding of the molecular mechanisms by which cadherin/catenin biomechanical signaling control the morphogenesis and homeostasis of stratifying epithelia.

皮肤表皮是一种自我更新的分层上皮，对皮肤屏障功能至关重要。基底表皮干细胞平衡自我更新与其后代的时空控制分化程序，伴随着空间协调的细胞形状变化。然而，这些形状变化是否控制定位和细胞命运尚不清楚。经典的钙粘蛋白偶联细胞间粘附力产生肌动球蛋白细胞骨架在专门的粘附连接（AJs）。因此，这些连接允许细胞在细胞之间传递力，以协调细胞形状变化和细胞反应。在SPP的前一阶段，我们将AJs中的E-cadherin鉴定为力传感和转导蛋白，其协调信号传导和机械响应以调节初始表皮分化步骤以及最终屏障形成。E-钙粘蛋白通过不同AJ机械状态的组织极化和差异皮质肌动蛋白网络组织来实现。下一个SPP阶段的总体目标是确定AJs如何控制F-肌动蛋白组织的不同状态，并询问这些状态是否以及如何将细胞位置与细胞命运和功能相结合。总之，提出的实验可能有助于更好地理解钙粘蛋白/连环蛋白生物力学信号控制分层上皮的形态发生和稳态的分子机制。