Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion

Chrystian Junqueira Alves, Rafael Dariolli, Jonathan Haydak, Sangjo Kang, Theodore Hannah, Robert J. Wiener, Stefanie DeFronzo, Rut Tejero, Gabriele L. Gusella, Aarthi Ramakrishnan, Rodrigo Alves Dias, Alexandre Wojcinski, Santosh Kesari, Li Shen, Eric A. Sobie, José Paulo Rodrigues Furtado de Mendonça, Evren U. Azeloglu, Hongyan Zou, Roland H. Friedel

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Article number6019
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021

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