The Molecular Basis of Radial Intercalation during Tissue Spreading in Early Development

Radial intercalation is a fundamental process responsible for the thinning of multilayered tissues during large-scale morphogenesis; however, its molecular mechanism has remained elusive. Using amphibian epiboly, the thinning and spreading of the animal hemisphere during gastrulation, here we provide evidence that radial intercalation is driven by chemotaxis of cells toward the external layer of the tissue. This role of chemotaxis in tissue spreading and thinning is unlike its typical role associated with large-distance directional movement of cells. We identify the chemoattractant as the complement component C3a, a factor normally linked with the immune system. The mechanism is explored by computational modeling and tested in vivo, ex vivo, and in vitro. This mechanism is robust against fluctuations of chemoattractant levels and expression patterns and explains expansion during epiboly. This study provides insight into the fundamental process of radial intercalation and could be applied to a wide range of morphogenetic events.