New Genes Controlling Neural Stem Cell Differentiation

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Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify the molecular mechanisms regulating the transition from proliferation to differentiation. However, analyzing transcriptomes of individual cell types in complex tissues remains a challenge. We generated a RFP/GFP double-reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations in the developing mammalian cortex. Transcriptome sequencing of these three cell types revealed numerous uncharacterized protein-coding genes, several long non-coding RNAs as well as completely new genes with a highly specific and transient expression pattern. Our recent work provides the most comprehensive and quantitative trascriptome resource during the switch of neural stem from proliferation to differentiation to date and identifies a list of completely uncharacterized genes likely playing important roles during mammalian corticogenesis. The purpose of the current application is to perform the functional experiments needed to characterize the molecular mechanisms underlying the action of some of these candidate new genes providing more insight into neural stem cell regulation during tissue formation and homeostasis.