EphrinB2 coordinates the formation of a morphological boundary and cell epithelialization during somite segmentation

Abstract

During early morphogenesis, tissue segregation is often accompanied by changes in cell shape. To understand how such coordination is regulated, somitogenesis was used as a model. When a somite forms in the anterior end of the presomitic mesoderm, an intersomitic boundary (gap) emerges, and it is rapidly followed by cell epithelialization at this border. It has been known that the gap formation is regulated by intercellular signals. We here demonstrate that cMeso-1, the chicken homolog of mouse Mesp2, upregulates EphA4 in the cells located posteriorly to a forming boundary. This in turn activates EphrinB2-reverse signals in the anteriorly juxtaposed cells, where the EphrinB2 signal is sufficient to cause a gap formation and cell epithelialization cell-autonomously. During these processes, Cdc42 needs to be repressed via tyrosine phosphorylation of EphrinB2. This is the first demonstration that Ephrin-reverse signal acts as a platform that couples distinct morphogenetic changes in cell polarity and tissue shape.Ephrin ͉ Epithelialization ͉ Segmentation

Eph/ephrin interactions modulate muscle satellite cell motility and patterning

“…Gamma correction1.45 in A,C. Scale bars: 200m in A,B; 100m in C. (Durbin et al, 1998;Watanabe et al, 2009), hindbrain (Cooke et al, 2001;Cooke et al, 2005;Kemp et al, 2009) and skull (Twigg et al, 2004;Merrill et al, 2006).…”

“…In vitro, differentiating muscle satellite cells orient according to ephrin patterning Ephrin/Eph signaling is largely dependent on cell-cell contacts in order to create change in the directionality of a migrating cell; however, ephrin/Eph signaling also plays an important role in cellular segregation and patterning, as seen in the developing somite (Durbin et al, 1998;Watanabe et al, 2009) or the late embryonic forelimb (Swartz et al, 2001;Wada et al, 2003). We observed that elongated, possibly differentiating, satellite cells in the forelimb were uniformly oriented with respect to the axis of the stream exiting the limb bud (Fig.…”

Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme

“…S10). Expression of ephrin B2 (Efnb2), which encodes a known ligand of EphA4 signaling (Watanabe et al, 2009), was found in the caudal ND and the cloaca as well as in the pericloacal mesenchyme from E10.5 until E14.5 (Fig. 7C-F).…”

“…Intriguingly, reverse ephrin B2 signaling has been implicated in the control of epithelial cell adhesion in urorectal maturation by promoting tubularization of the urethra and septation of the urinary and the anorectal system (Dravis et al, 2004). Fifth, although EphA receptors preferentially bind to ephrin A ligands, ephrin B2 has been described as a ligand for EphA4 in some contexts (Watanabe et al, 2009); ephrin B2 binding to EphA7 still needs to be validated on the biochemical level. Last, and most importantly, conditional deletion of Efnb2 in the ND phenocopied the urinary tract defects of DKO embryos to a substantial extent, including blind or ectopically ending ureters, delayed CND removal, lack or delayed ND insertion and downregulation of Gata3/Lhx1/Ret in the caudal ND.…”

The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite

“…Recently, we and others have suggested that the Mesp2 downstream events, such as the activation of ephrin-EphA4 signaling and the formation of a Tbx6 protein boundary, were more important for segmental border formation (Watanabe et al, 2009;Oginuma et al, 2008;Nakajima et al, 2006). In Lfng -/-embryos, the expression of EphA4 and the Tbx6 protein boundary were found to be diffuse or randomized (Fig.…”