Tissue maintenance and repair depend on stem cells that replenish cellular compartments reduced by physiological turnover or disease. Despite the essential function and unavoidable attrition of the enteric nervous system, a major branch of the peripheral nervous system that controls digestive physiology and gut homeostasis, the mechanisms controlling its cellular integrity and regeneration remain unknown. We will test the hypothesis that mammalian enteric glial cells (EGCs) exhibit neural stem cell activity and determine whether this is a property of a defined EGC sublineage or can be exhibited by a wider population of EGCs. As a first step, we will define the transcriptional hetrogeneity of EGCs and uncover the dynamic behaviour of moleculary defined supopulations during homeostasis or in response to gut pathology. Quantitive analysis and intavital imaging will inform the dynamics of EGCs within the gut microenvironment. The generation and functinal integration of enteric neurons into intestinal neural circuits will also be analysed.Finally, we will characterise niche signals and cell intrinsic transcriptional programmes that control fate decisions of EGCs, namely their choice to remain quiescent, enter the cell cycle and differentiate into neurons. Our work will advance the fields of neural stem cells, glia cell biology and gastroenterology. The gastrointestinal system is essential for digestive function and health. Not surprisingly, the complex physiological processes of digestive function are controlled by intricate regulatory systems, including vast neural networks that are embedded within the wall of the entire gastrointestinal tract. As in other parts of the nervous system, it is expected that the neural networks of the intestines are very dynamic and at least some of their cells are lost due to normal attrition or disease. Nevertheless, we know very little about the mechanisms that maintain the nervous system of the gut in good functional order and the cell types that are likely to be mobilised to replace potential intestinal neural cell losses. In our studies we will use a range of experimental approaches to characterise the dynamic behaviour of neural cell networks of the gut and understand the biological mechanisms that control their maintenance and regeneration in adult life.