Camsap2a regulates actomyosin flow and Rab5ab-mediated macropinocytosis in the yolk cell during zebrafish epiboly

In zebrafish, epiboly is a major morphogenic event during gastrulation, characterized by the thinning and spreading of the embryonic blastoderm to internalize the underlying extra-embryonic yolk cell. This movement is driven by the yolk cell, which generates motile force through actomyosin flow that engages a circumferential contractile band, pulling the attached blastoderm vegetally. Localized macropinocytosis of the yolk cell, another actin-driven process, also contributes to epiboly progression by removing yolk membrane ahead of the advancing blastoderm. The molecular mechanisms coordinating these processes are elusive. Here, we identified Camsap2a, a non-centrosomal, microtubule-stabilizing protein, as a regulator of actin-dependent processes in the yolk cell during epiboly. Epiboly is delayed in camsap2a mutant embryos, which exhibit reduced macropinocytosis as well as impaired actin flow, contractile band formation and function. We show that Camsap2a functions in actin regulation upstream of the small GTPase Rab5ab, as constitutively active Rab5ab rescues the defects in macropinocytosis, actomyosin band formation and epiboly. Our work provides new insights into the molecular control of epiboly and further implicates membrane dynamics as an important contributor to the process.