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

Nat Commun. 2021 Oct 14;12(1):6019. doi: 10.1038/s41467-021-26296-7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins
  • Actomyosin / metabolism*
  • CRISPR-Cas Systems
  • Cell Adhesion / physiology*
  • Cell Differentiation
  • Cell-Matrix Junctions / metabolism
  • Cytoskeleton / metabolism*
  • Embryonic Stem Cells
  • Gene Editing
  • Gene Expression
  • Humans
  • Mechanotransduction, Cellular
  • Morphogenesis
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells
  • Semaphorins
  • Signal Transduction
  • Stem Cells / metabolism*


  • Actins
  • Nerve Tissue Proteins
  • PLXNB2 protein, human
  • Semaphorins
  • Actomyosin