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Nat Commun ; 12(1): 6019, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650052

RESUMO

During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosin contractility, leading to changes in cell stiffness and cytoskeletal tension, as well as cell-cell and cell-matrix adhesion. We have delineated the functional domains of Plexin-B2, RAP1/2 effectors, and the signaling association with ERK1/2, calcium activation, and YAP mechanosensor, thus providing a mechanistic link between Plexin-B2-mediated cytoskeletal tension and stem cell physiology. Plexin-B2-deficient stem cells exhibit premature lineage commitment, and a balanced level of Plexin-B2 activity is critical for maintaining cytoarchitectural integrity of the developing neuroepithelium, as modeled in cerebral organoids. Our studies thus establish a significant function of Plexin-B2 in orchestrating cytoskeletal tension and cell-cell/cell-matrix adhesion, therefore solidifying the importance of collective cell mechanics in governing stem cell physiology and tissue morphogenesis.


Assuntos
Actomiosina/metabolismo , Adesão Celular/fisiologia , Citoesqueleto/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco/metabolismo , Actinas , Sistemas CRISPR-Cas , Diferenciação Celular , Junções Célula-Matriz/metabolismo , Células-Tronco Embrionárias , Edição de Genes , Expressão Gênica , Humanos , Mecanotransdução Celular , Morfogênese , Células-Tronco Neurais , Semaforinas , Transdução de Sinais
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