摘要：Summarym6A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m6A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate thatYthdf1andYthdf2double deletion but not individual knockout recapitulates the phenotype ofMettl14knockout in cortex. In addition, we find thatMettl14knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced whenYthdf1,Ythdf2, andYthdf3are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate m6A regulation of cortical and retinal neurogenesis.Graphical abstractDisplay OmittedHighlights•YTHDF1 and YTHDF2 have redundant functions in m6A regulation of cortical neurogenesis•m6A modification plays a critical role in retinal neurogenesis•OnlyYthdf1,Ythdf2, andYthdf3triple deletion disrupts retinal neurogenesis•YTHDF1 and YTHDF2 share a large pool of target mRNAs related to neurogenesisMolecular biology; Molecular Genetics; Neuroscience; Molecular neuroscience.
