Barrios A, Poole RJ, Durbin L, Brennan C, Holder N, Wilson SWEph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol 13:1571-1582

Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Current Biology (Impact Factor: 9.57). 10/2003; 13(18):1571-82. DOI: 10.1016/j.cub.2003.08.030
Source: PubMed


During somitogenesis, segmental patterns of gene activity provide the instructions by which mesenchymal cells epithelialize and form somites. Various members of the Eph family of transmembrane receptor tyrosine kinases and their Ephrin ligands are expressed in a segmental pattern in the rostral presomitic mesoderm. This pattern establishes a receptor/ligand interface at each site of somite furrow formation. In the fused somites (fss/tbx24) mutant, lack of intersomitic boundaries and epithelial somites is accompanied by a lack of Eph receptor/Ephrin signaling interfaces. These observations suggest a role for Eph/Ephrin signaling in the regulation of somite epithelialization.
We show that restoration of Eph/Ephrin signaling in the paraxial mesoderm of fss mutants rescues most aspects of somite morphogenesis. First, restoration of bidirectional or unidirectional EphA4/Ephrin signaling results in the formation and maintenance of morphologically distinct boundaries. Second, activation of EphA4 leads to the cell-autonomous acquisition of a columnar morphology and apical redistribution of beta-catenin, aspects of epithelialization characteristic of cells at somite boundaries. Third, activation of EphA4 leads to nonautonomous acquisition of columnar morphology and polarized relocalization of the centrosome and nucleus in cells on the opposite side of the forming boundary. These nonautonomous aspects of epithelialization may involve interplay of EphA4 with other intercellular signaling molecules.
Our results demonstrate that Eph/Ephrin signaling is an important component of the molecular mechanisms driving somite morphogenesis. We propose a new role for Eph receptors and Ephrins as intercellular signaling molecules that establish cell polarity during mesenchymal-to-epithelial transition of the paraxial mesoderm.

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    • "The intercalation of core eye field cells into the nascent epithelium of the evaginating optic vesicles constitutes an unusual MET. Other well-studied METs such as formation of the renal and gut epithelium (Dush and Nascone-Yoder, 2013; Urban et al., 2006; Vize et al., 1997) and somite formation from the presomitic mesoderm (Barrios et al., 2003; Watanabe et al., 2009) involve the establishment of an epithelium from a homogeneous population of mesenchymal cells. Perhaps comparable to the scenario we describe in the eye is the mechanism proposed to underlie gut formation in frogs (Dush and Nascone-Yoder, 2013) or lumen formation during secondary neurulation in chick, where it is thought that the cells in the center of the cord intercalate in between the already epithelialized cells of the outer neural layer (Schoenwolf and Delongo, 1980). "
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    ABSTRACT: Using high-resolution live imaging in zebrafish, we show that presumptive eye cells acquire apicobasal polarity and adopt neuroepithelial character prior to other regions of the neural plate. Neuroepithelial organization is first apparent at the margin of the eye field, whereas cells at its core have mesenchymal morphology. These core cells subsequently intercalate between the marginal cells contributing to the bilateral expansion of the optic vesicles. During later evagination, optic vesicle cells shorten, drawing their apical surfaces laterally relative to the basal lamina, resulting in further laterally directed evagination. The early neuroepithelial organization of the eye field requires Laminin1, and ectopic Laminin1 can redirect the apicobasal orientation of eye field cells. Furthermore, disrupting cell polarity through combined abrogation of the polarity protein Pard6γb and Laminin1 severely compromises optic vesicle evagination. Our studies elucidate the cellular events underlying early eye morphogenesis and provide a framework for understanding epithelialization and complex tissue formation.
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    • "Their complementary expression (Fig. 1) suggests that an interaction between Ephs and Ephrins occurs at the edge the eye field and this would be consistent with the presence of a cell affinity boundary at this location. Other morphogenetic processes associated with boundary formation, such as hindbrain and presomitic mesoderm segmentation in vertebrates, or compartment boundary formation during Drosophila segmentation and imaginal disc development, are associated with the accumulation of F-actin and phosphorylated light chain myosin II (Aliee et al., 2012; Barrios et al., 2003; Cooke et al., 2001; Landsberg et al., 2009; Monier et al., 2010). Indeed, at rhombomere and somite boundaries, the activity of the Eph/Ephrin pathway is upstream of the accumulation of F-actin and phosphorylated light chain myosin II (Cooke et al., 2001; Jülich et al., 2009; Watanabe et al., 2009), suggesting that the localisation of these molecules might be indicative of Eph/Ephrin activity. "
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    • "During MET, changes in cell fate result in the accumulation of cell adhesion complexes in a latero-apical domain, and promotes the localization of the nucleus in the basal part of the cell and the centrosome in the apical part (Barrios et al., 2003). These changes are also observed during optic vesicle evagination, including the accumulation of ZO-1 in the latero-apical part of the cells. "
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