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Epiboly is an evolutionary conserved morphogenetic massive cell movement in zebrafish that initiates at the onset of gastrulation. The regulation of cell adhesion/cohesion of blastoderm cells during this developmental stage is essential for the coordinated cell movements that characterize gastrulation. Here we show that inhibition of NADPH oxidase (Nox) activity leads to a significant delay in epiboly progression, displays altered E-cadherin and F-actin localization at the enveloping layer (EVL) cell margins and a significant decrease in embryo survival; suggesting that EVL cells have increased endosomal endocytosis. We confirmed this effect since the VAS2870 effects are fully rescued by down-regulating dynamin 2 activity. In addition, we show that proteasome pharmacological inhibition partially rescues the effects on epiboly due to Nox activity inhibition. Overall, our results show that Nox derived reactive oxygen species participate in the regulation of E-cadherin trafficking required for epiboly progression during early zebrafish development.

Molecular oxygen (O2), reactive oxygen species (ROS), and associated redox networks are cornerstones of aerobic life, these molecules and networks have gained recognition as fundamental players in mechanisms that regulate the development of multicellular organisms. First, we present a brief review in which we provide a historical description of some relevant discoveries that led to this recognition. We also discuss that despite its abundance in nature, oxygen is a limiting factor, and its high availability variation impacted the evolution of adaptive mechanisms to guarantee the proper development of diverse species under such extreme environments. Finally, some examples when oxygen and ROS were identified as relevant for the control of developmental processes are discussed. We take into account not only the current knowledge on animal redox developmental biology, but also briefly discuss potential scenarios on the origin and evolution of redox developmental mechanisms and the importance of the ever-changing environment.

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