Radial Glia as Neurodevelopmental Mediators Of Gut Microbiota Signals

Brain development is an intricately orchestrated process, that is sensitive to the influence of peripheral processes. One such peripheral factor known to have multiple roles in host physiology, is the gut microbiota: the ecosystem of symbiotic microorganisms that populate our gastrointestinal tract. Disruption of the gut microbiota has been associated with neurodevelopmental and neuropsychiatric disorders. However, the mechanisms through which the gut microbiota could influence brain development, and thus potentially lead to cognitive and behavioural deficits, remain to be elucidated. RADIOGUT aims to mechanistically understand the interactions between the gut microbiota, and brain neurodevelopment at molecular and cellular levels. To accomplish this, we will employ distinct models of early-life microbiota disruption in mice and assess the impact on neurodevelopment combining explant cultures with microbial metabolites, and an integrated multi-omics analysis. We will identify key microbial metabolites that modulate neurodevelopment, discern their signalling mechanisms and their potential to rescue neurodevelopmental deficits as well as later life aberrant behaviours. RADIOGUT will explore for the first time how the primary neural stem cells in the brain, the radial glia, can act as cellular sensors of microbial signals that modulate neurodevelopment. It will fill a large gap in the understanding of microbiota-gut-brain axis development and its communication code, as well as deliver tangible future translational value.