RESUMO
Cell polarization enables zygotes to acquire spatial asymmetry, which in turn patterns cellular and tissue axes during development. Local modification in the actomyosin cytoskeleton mediates spatial segregation of partitioning-defective (PAR) proteins at the cortex, but how mechanical changes in the cytoskeleton are transmitted to PAR proteins remains elusive. Here we uncover a role of actomyosin contractility in the remodelling of PAR proteins through cortical clustering. During embryonic polarization in Caenorhabditis elegans, actomyosin contractility and the resultant cortical tension stimulate clustering of PAR-3 at the cortex. Clustering of atypical protein kinase C (aPKC) is supported by PAR-3 clusters and is antagonized by activation of CDC-42. Cortical clustering is associated with retardation of PAR protein exchange at the cortex and with effective entrainment of advective cortical flows. Our findings delineate how cytoskeleton contractility couples the cortical clustering and long-range displacement of PAR proteins during polarization. The principles described here would apply to other pattern formation processes that rely on local modification of cortical actomyosin and PAR proteins.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimologia , Proteínas de Ciclo Celular/metabolismo , Polaridade Celular , Citoesqueleto/enzimologia , Proteínas de Ligação ao GTP/metabolismo , Mecanotransdução Celular , Proteínas de Membrana/metabolismo , Actomiosina/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Embrião não Mamífero/enzimologia , Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Proteínas de Membrana/genética , Camundongos , Microscopia de Fluorescência , Microscopia de Vídeo , Células NIH 3T3 , Fenótipo , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases , Estresse Mecânico , TransfecçãoRESUMO
The generation of a functional organism from a single, fertilized ovum requires the spatially coordinated regulation of diverse cell identities. The establishment and precise arrangement of differentiated cells in developing embryos has, historically, been extensively studied by geneticists and developmental biologists. While chemical gradients and genetic regulatory networks are widely acknowledged to play significant roles in embryo patterning, recent studies have highlighted that mechanical forces generated by, and exerted on, embryos are also crucial for the proper control of cell differentiation and morphogenesis. Here we review the most recent findings in murine preimplantation embryogenesis on the roles of cortical tension in the coupling of cell-fate determination and cell positioning in 8-16-cell-stage embryos. These basic principles of mechanochemical coupling in mouse embryos can be applied to other pattern formation phenomena that rely on localized modifications of cell polarity proteins and actin cytoskeletal components and activities.