Unraveling the molecular mechanism regulated by Sox9 in cortical neural stem cell behavior and fate commitment

During mammalian cortical development, how different subtypes of projection neurons are generated by neural stem cells remains a major challenge. Over recent years, the expansion of RNA sequencing technologies has allowed the identification of heterogeneity within the progenitor pool. Understanding how this heterogeneity could participate in the control of cortical fate commitment is an exciting task. Here, we use single-cell RNA sequencing to describe the molecular characteristics of a subpopulation of RGCs that present reduced neurogenic behavior at early embryonic ages to later produce mostly upper layer neurons. Among the differentially expressed genes identified, functional experiments with the transcriptional factor Sox9 reproduced a similar phenotype, causing a neurogenic delay and an increase in the production of upper layer neurons at later ages. To uncover the molecular mechanism acting downstream of Sox9, we have performed RNA-seq of RGCs 24 hours after IUE in control and Sox9 overexpressing conditions. This approach has helped us identified the gene regulatory program of Sox9 in RGCs that could contribute to upper layer neuron generation.