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

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...

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Veröffentlicht in:The Journal of cell biology 2016-10, Vol.215 (2), p.217-229
Hauptverfasser: O'Neill, Audrey K, Kindberg, Abigail A, Niethamer, Terren K, Larson, Andrew R, Ho, Hsin-Yi Henry, Greenberg, Michael E, Bush, Jeffrey O
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container_end_page 229
container_issue 2
container_start_page 217
container_title The Journal of cell biology
container_volume 215
creator O'Neill, Audrey K
Kindberg, Abigail A
Niethamer, Terren K
Larson, Andrew R
Ho, Hsin-Yi Henry
Greenberg, Michael E
Bush, Jeffrey O
description 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.
doi_str_mv 10.1083/jcb.201604097
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subjects Actins - metabolism
Actomyosin - metabolism
Animals
Cell Count
Cell Differentiation
Cells
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Ephrin-B1 - metabolism
Green Fluorescent Proteins - metabolism
HEK293 Cells
Humans
Kinases
Mice
Models, Biological
Neuroepithelial Cells - cytology
Neuroepithelial Cells - metabolism
Receptors, Eph Family - metabolism
rho-Associated Kinases - metabolism
Rodents
Signal Transduction
Tissues
title Unidirectional Eph/ephrin signaling creates a cortical actomyosin differential to drive cell segregation
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