M6A writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish

Abstract

N6-Methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNAs that modulates mRNA metabolism and function. Most m6A modifications on mRNAs are catalyzed by a core writer complex consisting of a methyltransferase, Mettl3, and two ancillary components, Mettl14 and Wtap. Recent studies have demonstrated important roles of m6A in various physiological and pathological processes, such as stem cell multipotency, cell differentiation, and cancer progression. However, our knowledge about m6A in the retina is still lacking. In this study, we used zebrafish as a model vertebrate to study the function of the m6A modification during retinal development. We show that the three main components of the m6A writer complex, mettl3, mettl14 and wtap, are abundantly expressed in the developing zebrafish eyes, and that knocking down m6A writer complex in zebrafish embryos caused microphthalmia formation, delayed retinal progenitor cells differentiation and increased cell death. By examining the retinal developmental processes in m6A writer complex-deficient fish, we show that m6A modification regulates zebrafish retinal development through ensuring the timely differentiation and survival of the retinal progenitor cells.