m6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs

m(6)A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m(6)A readers, YTHDF1,YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when Ythdf1, Ythdf2, and Ythdf3 are 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 m(6)A regulation of cortical and retinal neurogenesis.

Automated summary

YTHDF1 and YTHDF2 play important roles in regulating mammalian neurogenesis through mediating m(6)A modification, and they are involved in the regulation of cortical and retinal neurogenesis.