Neurite

Neuroscience

Progenitor

Biology

Gene

Embryonic stem cell

Neurosphere

Stem cell

Cell biology

Neural stem cell

Genetics

Neurogenesis

Adult stem cell

Neural development

In vitro

Neocortex

Progenitor cell

Genome biology

N 6 -methyladenosine (m6A) modification in mRNAs was recently shown to be dynamically regulated, indicating a pivotal role in multiple developmental processes. Most recently, it was shown that the Mettl3-Mettl14 writer complex of this mark is required for the temporal control of cortical neurogenesis. The m6A reader protein Ythdf2 promotes mRNA degradation by recognizing m6A and recruiting the mRNA decay machinery.We show that the conditional depletion of the m6A reader protein Ythdf2 in mice causes lethality at late embryonic developmental stages, with embryos characterized by compromised neural development. We demonstrate that neural stem/progenitor cell (NSPC) self-renewal and spatiotemporal generation of neurons and other cell types are severely impacted by the loss of Ythdf2 in embryonic neocortex. Combining in vivo and in vitro assays, we show that the proliferation and differentiation capabilities of NSPCs decrease significantly in Ythdf2 -/- embryos. The Ythdf2 -/- neurons are unable to produce normal...

Ythdf2-mediated m6A mRNA clearance modulates neural development in mice