Collagen triple helix repeat containing 1a (Cthrc1a) regulates cell adhesion and migration during gastrulation in zebrafish

Highlights: • Cthrc1 is required for directed cell movements during gastrulation in zebrafish. • Cthrc1 regulates cell adhesion and migration on extracellular substratum. • Inhibition of Cthrc1 prevents the protrusive activity of migrating cells. • The cell surface localisation of secreted Cthrc1 is dependent on integrin β1. • Cthrc1 functionally interacts with integrin β1 in embryonic axis elongation. -- Abstract: Cell adhesion and migration are key cell behaviours during gastrulation in early embryos and metastasis in cancers. Cthrc1 is a secreted protein highly conserved among vertebrates; it is upregulated in injured and diseased arteries, as well as in malignant cancers. There is increasing evidence showing that its expression and activity are associated with cancer progression and inflammatory diseases. However, the mechanism by which it regulates cell migration, and its implication during early development remains unclear. Here we show that zebrafish Cthrc1a is expressed in hypoblast cells, and is required for cell adhesion and migration during gastrulation. Knockdown of cthrc1a in whole embryo inhibits epiboly and convergent extension movements, and reduces the elongation of anteroposterior axis. Cell adhesion assay indicates that Cthrc1a is necessary for mesendoderm cells to interact with fibronectin-coated substratum, and to extend polarised cellular protrusions. Moreover, secreted Cthrc1a proteins diffuse efficiently between blastoderm cells and are recruited by neighbouring cells in an integrin-dependent manner. Consistently, there exists a functional interaction between Cthrc1a and integrin β1 in anteroposterior axis elongation. These results provide insight into the function of Cthrc1a in the regulation of cell adhesion and migration during embryonic axis elongation.