Compared with the mesoderm, endoderm convergence and extension (C&E) events remain elusive. Now, Fang Lin and colleagues employ high-resolution imaging of a zebrafish sox17-reporter line to study endoderm C&E. They show that, during segmentation (6–12 somites), while migrating towards the midline, endoderm cells elongate and polarise along the mediolateral axis and intercalate. Then, between 12 and 18 somites, endoderm cells migrate ventrally and constrict apically to form a rod-like structure that later develops into the gut tube. Glypican 4 (Gpc4), which influences Wnt/planar cell polarity (PCP) signalling, is required for the planar polarisation of endodermal cells, because cell polarity and intercalation are impaired in gpc4–/– embryos. gpc4 deficiency disrupts Wnt/PCP signalling in endoderm cells, as determined by the loss of the anterior localisation of Vangl2 (a PCP component). In addition, gpc4-/- embryos exhibit increased cell-cell adhesion and Cadherin 2 (Cdh2) localisation at the membrane. The authors demonstrate that gpc4-/- embryos have decreased rab5c expression, which is required for Cdh2 endocytosis at the membrane. Importantly, Rab5c overexpression or Cdh2 suppression in gpc4-/- embryos partially rescues the endoderm defects. Taken together, these data indicate a model in which Gpc4-dependent Rab5c-mediated endocytosis of Cdh2 promotes cell intercalation and polarisation for endoderm C&E.
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