Unidirectional Eph/ephrin signaling creates a cortical actomyosin differential to drive cell segregation

J Cell Biol. 2016 Oct 24;215(2):217-229. doi: 10.1083/jcb.201604097. Epub 2016 Oct 17.

Abstract

Cell segregation is the process by which cells self-organize to establish developmental boundaries, an essential step in tissue formation. Cell segregation is a common outcome of Eph/ephrin signaling, but the mechanisms remain unclear. In craniofrontonasal syndrome, X-linked mosaicism for ephrin-B1 expression has been hypothesized to lead to aberrant Eph/ephrin-mediated cell segregation. Here, we use mouse genetics to exploit mosaicism to study cell segregation in the mammalian embryo and integrate live-cell imaging to examine the underlying cellular and molecular mechanisms. Our data demonstrate that dramatic ephrin-B1-mediated cell segregation occurs in the early neuroepithelium. In contrast to the paradigm that repulsive bidirectional signaling drives cell segregation, unidirectional EphB kinase signaling leads to cell sorting by the Rho kinase-dependent generation of a cortical actin differential between ephrin-B1- and EphB-expressing cells. These results define mechanisms of Eph/ephrin-mediated cell segregation, implicating unidirectional regulation of cortical actomyosin contractility as a key effector of this fundamental process.

MeSH terms

  • Actins / metabolism
  • Actomyosin / metabolism*
  • Animals
  • Cell Count
  • Cell Differentiation*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Ephrin-B1 / metabolism*
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Biological
  • Neuroepithelial Cells / cytology*
  • Neuroepithelial Cells / metabolism
  • Receptors, Eph Family / metabolism*
  • Signal Transduction*
  • rho-Associated Kinases / metabolism

Substances

  • Actins
  • Ephrin-B1
  • Green Fluorescent Proteins
  • Actomyosin
  • Receptors, Eph Family
  • rho-Associated Kinases