Unequal mitochondrial segregation promotes asymmetric fates during neurogenesis

Asymmetric cell division plays a critical role during vertebrate neurogenesis by generating neuronal cells while maintaining a pool of progenitors. It relies on unequal distribution of cell fate determinants during progenitor division. Here, we use live imaging in the chick embryonic neuroepithelium to demonstrate that mitochondria behave as asymmetric fate determinants during mitosis. We show that the frequency of unequal distribution of mitochondria increases in parallel with the rate of asymmetric divisions during development. Furthermore, fate tracking experiments reveals that following progenitor division, a cell inheriting fewer mitochondria than its sister consistently differentiates into a neuron. We set up a chemogenetic approach to experimentally displace mitochondria specifically during mitosis to force their unequal inheritance and find that this drives premature neuronal differentiation. In this work, we establish a direct causal relationship between unequal mitochondrial inheritance and the asymmetric fate of sister cells in vivo, revealing a pivotal mechanism for neurogenesis.