SummaryBrain structure and size requires precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size as seen in microcephaly. Here we demonstrate that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number, and genomic stability. In utero rescue experiments revealed that a key function of Magoh is to control levels of the microcephaly-associated protein, LIS1, during neurogenesis. This study uncovers new requirements for the EJC in brain development, NSC maintenance, and mitosis, thus implicating this complex in the pathogenesis of microcephaly.
Highlights d Histone lysine crotonylation (Kcr) oscillates in the yeast metabolic cycle (YMC) d Deregulation of crotonyl-CoA metabolism results in YMC defects d Taf14, a histone Kcr reader, is needed for transcription oscillations in the YMC d Kcr reading by Taf14 reduces growth gene expression during nutrient limitation
The interaction of two oscillators (cell division cycle and yeast metabolic cycle) with different frequencies is studied. Cell cycle Start is coupled with the initiation of high oxygen consumption and breakdown of storage carbohydrates across diverse strains and different growth rates.
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