scholarly journals Interplay of Eph-Ephrin Signalling and Cadherin Function in Cell Segregation and Boundary Formation

Author(s):  
David G. Wilkinson

The segregation of distinct cell populations to form sharp boundaries is crucial for stabilising tissue organisation, for example during hindbrain segmentation in craniofacial development. Two types of mechanisms have been found to underlie cell segregation: differential adhesion mediated by cadherins, and Eph receptor and ephrin signalling at the heterotypic interface which regulates cell adhesion, cortical tension and repulsion. An interplay occurs between these mechanisms since cadherins have been found to contribute to Eph-ephrin-mediated cell segregation. This may reflect that Eph receptor activation acts through multiple pathways to decrease cadherin-mediated adhesion which can drive cell segregation. However, Eph receptors mainly drive cell segregation through increased heterotypic tension or repulsion. Cadherins contribute to cell segregation by antagonising homotypic tension within each cell population. This suppression of homotypic tension increases the difference with heterotypic tension triggered by Eph receptor activation, and it is this differential tension that drives cell segregation and border sharpening.

2020 ◽  
Vol 295 (12) ◽  
pp. 3932-3944 ◽  
Author(s):  
Melany J. Wagner ◽  
Marilyn S. Hsiung ◽  
Gerald D. Gish ◽  
Rick D. Bagshaw ◽  
Sasha A. Doodnauth ◽  
...  

Eph receptors are a family of receptor tyrosine kinases that control directional cell movement during various biological processes, including embryogenesis, neuronal pathfinding, and tumor formation. The biochemical pathways of Eph receptors are context-dependent in part because of the varied composition of a heterotypic, oligomeric, active Eph receptor complex. Downstream of the Eph receptors, little is known about the essential phosphorylation events that define the context and instruct cell movement. Here, we define a pathway that is required for Eph receptor B2 (EphB2)–mediated cell sorting and is conserved among multiple Eph receptors. Utilizing a HEK293 model of EphB2+/ephrinB1+ cell segregation, we found that the scaffold adaptor protein SH2 domain–containing adaptor protein B (Shb) is essential for EphB2 functionality. Further characterization revealed that Shb interacts with known modulators of cytoskeletal rearrangement and cell mobility, including Nck adaptor protein (Nck), p120-Ras GTPase-activating protein (RasGAP), and the α- and β-Chimaerin Rac GAPs. We noted that phosphorylation of Tyr297, Tyr246, and Tyr336 of Shb is required for EphB2–ephrinB1 boundary formation, as well as binding of Nck, RasGAP, and the chimaerins, respectively. Similar complexes were formed in the context of EphA4, EphA8, EphB2, and EphB4 receptor activation. These results indicate that phosphotyrosine-mediated signaling through Shb is essential in EphB2-mediated heterotypic cell segregation and suggest a conserved function for Shb downstream of multiple Eph receptors.


2015 ◽  
Vol 7 (3) ◽  
pp. 298-312 ◽  
Author(s):  
Sahar Javaherian ◽  
Elisa D'Arcangelo ◽  
Benjamin Slater ◽  
Teresa Zulueta-Coarasa ◽  
Rodrigo Fernandez-Gonzalez ◽  
...  

Separation of phenotypically distinct cell populations is necessary to ensure proper organization and function of tissues and organs therefore understanding fundamental mechanisms that drive this cell segregation is important. In this work, authors present an in vivo model system that accurately recapitulates important aspects of cell segregation in vivo and allows dissection of cell behaviours driving cell segregation.


2018 ◽  
Vol 98 (1) ◽  
pp. 391-418 ◽  
Author(s):  
Deniz Atasoy ◽  
Scott M. Sternson

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.


2014 ◽  
Vol 83 (2) ◽  
pp. 82-92 ◽  
Author(s):  
Georgina Gáti ◽  
Dávid Lendvai ◽  
Tomas Hökfelt ◽  
Tibor Harkany ◽  
Alán Alpár

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 991-1004 ◽  
Author(s):  
L.K. Gont ◽  
H. Steinbeisser ◽  
B. Blumberg ◽  
E.M. de Robertis

Three lines of evidence suggest that tail formation in Xenopus is a direct continuation of events initiated during gastrulation. First, the expression of two gene markers, Xbra and Xnot2, can be followed from the blastopore lip into distinct cell populations of the developing tailbud. Second, the tip of the tail retains Spemann's tail organizer activity until late stages of development. Third, lineage studies with the tracer DiI indicate that the cells of the late blastopore are fated to form specific tissues of the tailbud, and that intercalation of dorsal cells continues during tail elongation. In particular, the fate map shows that the tip of the tail is a direct descendant of the late dorsal blastopore lip. Thus, the tailbud is not an undifferentiated blastema as previously thought, but rather consists of distinct cell populations which arise during gastrulation.


Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 61-62
Author(s):  
S. E. Wedden

The discussion following the session on evolution and morphogenesis of the head and face concentrated upon two major issues: (1) How can one test models of development, particularly at biochemical and molecular levels? (2) Are the cell populations of the early facial primordia heterogeneous and when might this heterogeneity arise? The Chairman, J. Z. Young (London), had suggested in his introductory remarks that research into craniofacial development was at last becoming more specialized, having previously dealt with principles and model systems rather than with issues of practical importance. The ensuing lectures clearly demonstrated the direction and advances in current research, both in evolutionary aspects and at the level of morphogenesis. Robert Greene (Philadelphia) opened the general discussion. He emphasized the need to examine biochemical and molecular aspects of craniofacial development. In his view, the conceptual chasm between the gene and metazoan embryogenesis was wide and deep and had remained so in recent years.


2020 ◽  
Vol 14 ◽  
Author(s):  
Peter A. Groblewski ◽  
Douglas R. Ollerenshaw ◽  
Justin T. Kiggins ◽  
Marina E. Garrett ◽  
Chris Mochizuki ◽  
...  

2002 ◽  
Vol 87 (6) ◽  
pp. 2706-2715 ◽  
Author(s):  
Philippa T. K. Saunders ◽  
Michael R. Millar ◽  
Sheila Macpherson ◽  
D. Stewart Irvine ◽  
Nigel P. Groome ◽  
...  

1987 ◽  
Vol 253 (2) ◽  
pp. C323-C328 ◽  
Author(s):  
H. Holthofer ◽  
B. A. Schulte ◽  
G. Pasternack ◽  
G. J. Siegel ◽  
S. S. Spicer

The morphologically heterogeneous cell populations in the collecting ducts of the rat kidney were studied using immunocytochemical detection of Na+-K+-ATPase and the anion channel (band 3) glycoprotein. Both enzymes were localized to the basal aspect of separate and morphologically distinct subpopulations of cells in various segments of the collecting duct. Na+-K+-ATPase appeared to be present exclusively in principal cells as identified by their morphology, whereas band 3 antibodies reacted only with intercalated cells. However, 5-20% of cells with the morphological characteristics of intercalated cells failed to react with either antisera in various segments of collecting ducts. As band 3 glycoprotein serves in exchanging intracellular bicarbonate for chloride, it is highly likely that the cells positive for this antigen secrete protons. The method introduced here appears thus useful for distinguishing between principal and intercalated cells by differences in their enzyme content and further for revealing two subpopulations of intercalated cells. This method promises to provide a useful approach for studying the principal and intercalated cell populations in various metabolic states.


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