Unequal mitochondrial segregation promotes asymmetric fates during neurogenesis

Asymmetric divisions of vertebrate neural progenitors are critical for generating neurons while preserving the stem cell pool, ensuring proper central nervous system development. It was previously shown that the post-mitotic remodeling of mitochondrial activity in daughter cells influences neural fates. In this study, we demonstrate that unequal distribution of mitochondria during asymmetric mitosis plays a decisive role in triggering this differentiation process. Using live imaging to monitor mitochondrial segregation in individual progenitors and track their progeny’s fate within embryonic neural tissue, we show that daughter cells inheriting fewer mitochondria consistently differentiate into neurons, whereas their sibling receiving more mitochondria retains the progenitor status. Furthermore, experimental displacement of mitochondria during mitosis to force their unequal inheritance was sufficient to drive premature neuronal differentiation. Our findings establish a direct causal relationship between unequal mitochondrial inheritance and the asymmetric fate of sister cells in vivo , uncovering a key mechanism in neural development.