MITOCHONDRIA AND METABOLISM IN THE EVOLUTION OF CORTICAL DEVELOPMENT

Brains exist in a wide variety of sizes and shapes across phylogeny. This is determined largely by cell production during development. The early proliferation of neural progenitor cells is followed by the generation of postmitotic neurons (direct neurogenesis), or intermediate amplifying progenitor cells that later go on to produce neurons (indirect neurogenesis). The choice between direct and indirect neurogenesis affects the overall neuronal output and its temporal dynamics. The balance between neurogenesis modes varies significantly across species. Species with smaller cortices, such as reptiles and small birds, primarily generate neurons by direct neurogenesis, whereas mammals, such as mouse, rely on higher levels of indirect neurogenesis, particularly during early stages. Many publications have uncovered the role of metabolism in neural stem cell proliferation and neuronal differentiation, but only recently the focus extended to the role of mitochondrial dynamics in these processes. Here we investigate in detail mitochondrial morphology and dynamics in neural progenitor cells of mouse and chick using super-resolution microscopy and ex vivo time-lapses. We uncover fundamental differences between these two species with very different balance of neurogenesis modes. Our transcriptomic analysis of mitochondrial and metabolic protein genes reveals candidates linked to high rates of direct neurogenesis. Ongoing work aims to unveil how the combination of mitochondrial fusion/fission, compartmentalization, accumulation and metabolic regime determine the choice and balance of neurogenic modes, and its conservation across amniotes.