Deciphering the signalling events that control the dynamics of neural progenitors

Although most neurogenesis occurs during embryonic periods, dedicated neural stem cells persist in specialised niches of the mammalian brain (dentate gyrus and subventricular zone). Here, maintaining the correct balance between quiescent and active states ensures lifelong neurogenesis. In contrast to the brain, neural stem cell niches have not been identified in the gut. However, in adult zebrafish enteric glia can undergo neurogenesis. Moreover, although adult mammalian glia does not give rise to neurons at homeostasis, we find they can undergo efficient neurogenesis in culture, without the addition of reprogramming factors. We propose that the differential neurogenic activities of these cells are a consequence of their distinct environment. To explore this hypothesis, we will perform high-resolution spatial transcriptomics across time (embryonic and adult samples), species (mouse and zebrafish) and organs (brain and gut). This will allow us to decipher how cell-cell contacts impact on the transcriptomic state and neuronal output of the cells, and to infer downstream signalling pathways that control the bidirectional transitions between ‘activated’ and ‘quiescent’ states. We will then validate these findings by manipulating the environment in cell culture models. Findings from this research could advance fundamental knowledge and the development of therapies for neurodegenerative diseases.