Mechanobiology of apoptotic cell clearance in the early embryo
Spontaneous cellular errors can lead to cell death already in early embryo development. Apoptotic cell clearance is thus essential for tissue homeostasis and embryo survival. The outer epithelial layer of the embryo establishes an innate immune function and mediates the clearance of apoptotic cells....
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/694350 |
| Acceso en línea: | http://hdl.handle.net/10803/694350 |
| Access Level: | acceso embargado |
| Palabra clave: | Apoptotic cell clearance Non-professional epithelial phagocytosis E-cadherin Mechanobiology Embryonic error correction Neteja fagocítica de cèl·lules apoptòtiques Fagocitosis no professional de les cèl·lules epitelials E-caderina Mecanobiologia Correcció d’errors cel·lulars en embrions 576 |
| Sumario: | Spontaneous cellular errors can lead to cell death already in early embryo development. Apoptotic cell clearance is thus essential for tissue homeostasis and embryo survival. The outer epithelial layer of the embryo establishes an innate immune function and mediates the clearance of apoptotic cells. How mechanical forces and physical properties of apoptotic cells influence phagocytic tissue clearance has not been addressed in vivo. In this work, we systematically studied how biophysical target properties – as cell size, mechanics and ligand density – control phagocytosis and protrusion plasticity in epithelia. We identified that mechanical forces generated during epithelia-target interaction promote apoptotic cell fragmentation, ensuring efficient phagocytic clearance. We further discovered apoptotic cell softening as a pro-phagocytic signal. We identified that E-cadherin and its downstream effectors α-catenin and p120-catenin are key regulators of actomyosin dynamics at the phagocytic synapse that mediate the mechanosensitive clearance of apoptotic cells. This represents a novel function of the cadherin-catenin complex in apoptotic cell clearance. |
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