Embryonic interneuron development underlies cortical function and its disruption contributes to neurological disease. Yet the mechanisms by which viable interneurons are produced from progenitors remain poorly understood. Here, we demonstrate dosage-dependent requirements of the exon junction complex component for interneuron genesis in mouse. Conditional ablation from interneuron progenitors, but not post-mitotic neurons, depletes cortical interneuron number through adulthood, with increased severity in homozygotes. Using live imaging, we discover that deficiency delays progenitor mitotic progression in a dosage-sensitive fashion, with 40% of homozygous progenitors failing to divide. This shows that is required in progenitors for both generation and survival of newborn progeny. Transcriptome analysis implicates p53 signaling; moreover, ablation in haploinsufficient progenitors rescues apoptosis, completely recovering interneuron number. In striking contrast, in homozygotes, loss fails to rescue interneuron number and mitotic delay, further implicating mitotic defects in interneuron loss. Our results demonstrate that interneuron development is intimately dependent upon progenitor mitosis duration and uncover a crucial post-transcriptional regulator of interneuron fate relevant for neurodevelopmental pathologies.This article has an associated 'The people behind the papers' interview.
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