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

• DOI: 10.1083/jcb.201604097
• Publication Date: 2016-10-17T14:35:16Z
• Authors: Audrey K. O’Neill; Abigail A. Kindberg; Terren K. Niethamer; Andrew R. Larson; Hsin-Yi Henry Ho; Michael E. Greenberg; Jeffrey O. Bush
• Keywords: 0301 basic medicine; 570; 1.1 Normal biological development and functioning; Green Fluorescent Proteins; Neuroepithelial Cells; Cell Count; Ephrin-B1; Medical and Health Sciences; Models, Biological; Article; Mice; 03 medical and health sciences; Models; Underpinning research; Receptors; 2.1 Biological and endogenous factors; Animals; Humans; Aetiology; Research Articles; Receptors, Eph Family; rho-Associated Kinases; Mammalian; Eph Family; Cell Differentiation; Actomyosin; Biological Sciences; Biological; Embryo, Mammalian; Actins; HEK293 Cells; Embryo; Generic health relevance; Developmental Biology; Signal Transduction

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.