Regulatory roles of mitochondria and metabolism in human and mouse neurogenesis

Neurogenesis is the process by which dividing neural stem/progenitor cells (NSPCs) produce post-mitotic cells. The balance between self-renewal and differentiation is a highly controlled process under the influence of intrinsic and extrinsic factors. Previous studies have pointed to a model whereby cell fate is largely determined before the last mitosis. However, recent findings indicate that in the cerebral cortex mitochondrial dynamics have an impact on neurogenesis after the last cell division. Daughter cells with high levels of mitochondrial fusion undergo self-renewal, whereas those cells that will become neurons display mitochondrial fission. This defines a critical period during which cell fate can be changed following manipulation of mitochondria dynamics or metabolism. Intriguingly this critical period is doubled in human vs mouse stem cells, which could be linked to the higher self-renewing potential of human cortical progenitors. Here we focus on the differences in mitochondrial activity of progenitor cells during development and between different species. In addition, we aim to understand the impact of mitochondria-derived metabolites by which mitochondria and metabolism affect neural cell fate and temporal patterning.