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

Document Type

Article

Publication Date

10-14-2021

Publication Title

Nat Commun

Keywords

california; santa monica; jwci; pacific neuroscience; Actins; Actomyosin; CRISPR-Cas Systems; Cell Adhesion; Cell Differentiation; Cell-Matrix Junctions; Cytoskeleton; Embryonic Stem Cells; Gene Editing; Gene Expression; Humans; Mechanotransduction, Cellular; Morphogenesis; Nerve Tissue Proteins; Neural Stem Cells; Semaphorins; Signal Transduction; Stem Cells

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.

Clinical Institute

Neurosciences (Brain & Spine)

Clinical Institute

Cancer

Department

Neurosciences

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