Flotillins control zebrafish epiboly through their role in cadherin‐mediated cell–cell adhesion

Zebrafish gastrulation and particularly epiboly that involves coordinated movements of several cell layers is a dynamic process for which regulators remain to be identified. We show here that Flotillin 1 and 2, ubiquitous and highly conserved proteins, are required for epiboly. Flotillins knockdown compromised embryo survival, strongly delayed epiboly and impaired deep cell radial intercalation and directed collective migration without affecting enveloping layer cell movement. At the molecular level, we identified that Flotillins are required for the formation of E‐cadherin‐mediated cell–cell junctions. These results provide the first in vivo evidence that Flotillins regulate E‐cadherin‐mediated cell–cell junctions to allow epiboly progression. Short Communication: Collective cell migration, which enables fundamental processes in morphogenesis, tissue repair and cancer invasion, has long been known to be controlled by cell–cell adhesion molecules of the cadherin family. Using zebrafish and integrated cell biology approaches, we identified Flotillins as major regulator of this process during zebrafish epiboly, the first coordinated cell movement in most vertebrates that marks the onset of gastrulation.