Role of non-canonical Wnt/Planar Cell Polarity signaling in gut-endoderm morphogenesis

Endoderm is the deepest germ layer that contributes to the inner lining of the gastrointestinal tract. In addition, endoderm also contributes to the development of various organs and tissues such as heart, lungs and craniofacial structures. However, the underlying cellular and molecular mechanisms of this process are not fully understood. In zebrafish, convergence and extension (C&E) movements drive narrowing and elongation of naïve endodermal sheet into a gut-tube, during which gut endodermal cells exhibit polarized cell behaviors. Interestingly, all the posterior endodermal cells are polarized along the mediolateral axis of the embryo suggesting the presence of planar cell polarity (PCP), a phenomenon observed in many tissues during embryo development. A role for non-canonical Wnt/PCP(Wnt/PCP) components in gut-endoderm development is well established in various vertebrate models. Deficiency of Wnt/PCP signaling components such as glypican 4 (gpc4) and vang gogh like 2 (vangl2) disrupts polarized endodermal cell behaviors and impair endodermal PCP and C&E movements. Similar disruptions in PCP and C&E movements were also reported in other tissues such as mesoderm in Zebrafish gpc4^-/- and vangl2^-/- embryos. during gastrulation, however, the precise role of Gpc4 and Vangl2 in PCP is not fully understood. Our studies further demonstrate that Gpc4 and Vangl2 control N-cadherin mediated cell-cell adhesion and Rac-mediated protrusions respectively, to regulate polarized endodermal cell behaviors. Thus, our study uncovers a new mechanism by which Gpc4 and Vangl2 regulates planar cell polarity and reveals the role of Wnt/PCP signaling in endoderm morphogenesis.