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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Detalles Bibliográficos
Autor: Batet Palau, Marta
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
Descripción
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.