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

Autor: Terren K. Niethamer, Audrey K. O’Neill, Jeffrey O. Bush, Andrew R. Larson, Hsin-Yi Henry Ho, Abigail A. Kindberg, Michael E. Greenberg
Rok vydání: 2016
Předmět:
0301 basic medicine
Cellular differentiation
Cell
Neuroepithelial Cells
Cell Count
Medical and Health Sciences
Mice
Models
Receptors
2.1 Biological and endogenous factors
Aetiology
Research Articles
rho-Associated Kinases
Eph Family
Cell Differentiation
Actomyosin
Biological Sciences
Cell sorting
Cell biology
medicine.anatomical_structure
Embryo
embryonic structures
Signal transduction
Signal Transduction
animal structures
1.1 Normal biological development and functioning
Green Fluorescent Proteins
Ephrin-B1
Biology
Models
Biological

Article
03 medical and health sciences
Underpinning research
medicine
Animals
Humans
Ephrin
Actin
Receptors
Eph Family

Mammalian
HEK 293 cells
Erythropoietin-producing hepatocellular (Eph) receptor
Cell Biology
Embryo
Mammalian

Biological
Actins
biological factors
HEK293 Cells
030104 developmental biology
Generic health relevance
sense organs
Developmental Biology
Zdroj: The Journal of cell biology, vol 215, iss 2
The Journal of Cell Biology
ISSN: 1540-8140
0021-9525
DOI: 10.1083/jcb.201604097
Popis: Eph/ephrins drive cell segregation and boundary formation. O’Neill et al. discover that segregation is driven by unidirectional kinase-dependent EphB signaling. Unidirectional signaling generates a cortical actin differential between ephrin-B1– and EphB2-expressing cells and requires ROCK activity for 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 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.
Databáze: OpenAIRE