Mitochondrial dynamics after mitosis controls neuronal fate commitment.
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Developmental metabolic shifts drive neural stem cell amplification and differentiation.
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Metabolic intermediates impact neurogenesis through post-translational modifications.
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Loss of tricarboxylic acid cycle–associated genes impairs neurogenesis in the embryonic and adult brain.
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Species differences in mitochondria dynamics and function could be linked to the evolution of neurogenesis.
Abstract
Neural stem cells (NSCs) undergo massive molecular and cellular changes during neuronal differentiation. These include mitochondria and metabolism remodelling, which were thought to be mostly permissive cues, but recent work indicates that they are causally linked to neurogenesis. Striking remodelling of mitochondria occurs right after mitosis of NSCs, which influences the postmitotic daughter cells towards self-renewal or differentiation. The transitioning to neuronal fate requires metabolic rewiring including increased oxidative phosphorylation activity, which drives transcriptional and epigenetic effects to influence cell fate. Mitochondria metabolic pathways also contribute in an essential way to the regulation of NSC proliferation and self-renewal. The influence of mitochondria and metabolism on neurogenesis is conserved from fly to human systems, but also displays striking differences linked to cell context or species. These new findings have important implications for our understanding of neurodevelopmental diseases and possibly human brain evolution.
