Abstract
The segregation of cells with distinct regional identity underlies formation of a sharp border, which in some tissues serves to organise a boundary signaling centre. It is unclear whether or how border sharpness is coordinated with induction of boundary-specific gene expression. We show that forward signaling of EphA4 is required for border sharpening and induction of boundary cells in the zebrafish hindbrain, which we find both require kinase-dependent signaling, with a lesser input of PDZ domain-dependent signaling. We find that boundary-specific gene expression is regulated by myosin II phosphorylation, which increases actomyosin contraction downstream of EphA4 signaling. Myosin phosphorylation leads to nuclear translocation of Taz, which together with Tead1a is required for boundary marker expression. Since actomyosin contraction maintains sharp borders, there is direct coupling of border sharpness to boundary cell induction that ensures correct organisation of signaling centres.
Highlights
During embryo development, sharp borders form at the interface of adjacent tissues and between domains within tissues that have a different regional identity
It is likely that activation of other Eph receptors underlies increased phosphorylation of myosin light chain (pMLC) and boundary gene expression at the r1/r2, r5/r6 and r6/r7 borders that are not disrupted in the EphA4 mutants; for example, EphB4 which underlies cell segregation and has complementary expression to ephrinb2a (Chan et al, 2001; Cooke et al, 2001; Cooke et al, 2005)
The mechanical regulation of gene expression enables an interplay between morphogenesis and cell identity that contributes to tissue patterning (Chan et al, 2017; Kim et al, 2018; Xia et al, 2019)
Summary
Sharp borders form at the interface of adjacent tissues and between domains within tissues that have a different regional identity These borders are generated by cell segregation mechanisms that establish and maintain a precise organisation of tissues (Batlle and Wilkinson, 2012; Dahmann et al, 2011; Fagotto, 2014). The formation of a sharp and straight border enables such boundary signaling cells to be correctly organised (Dahmann and Basler, 1999). It remains unclear whether or how the induction of a signaling centre is coordinated with border sharpening. Studies of the vertebrate hindbrain found that Eph receptor and ephrin signaling is required both for border sharpening and the formation of boundary cells (Cooke et al, 2005; Terriente et al, 2012; Xu et al, 1995), raising the possibility that there is a mechanistic link
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