17-P017 Notchless regulates adult hematopoietic stem cell homeostasis

The enteric nervous system (ENS) is a complex network of neurons and glia within the gut wall which originate from neural crest cells. Self-renewing, multipotential ENS progenitors have been isolated from the gut of foetal as well as adult rodents, however, the identity of the ENS progenitor and the regulation of its neurogenic potential invivo, are currently unknown. Sox10 is an HMG-containing transcriptional regulator expressed in ENS progenitors and in glia but not in neurons. To lineally mark the progeny of Sox10-expressing cells, we used Sox10Cre; R26ReYFP transgenics. Our analysis shows that both the Sox10 neurons and the Sox10 glia cells are derived from Sox10-expressing progenitors. To examine the temporal regulation of the neurogenic potential of Sox10 ENS progenitors, we generated Sox10iCreER transgenics. Analysis of Sox10iCreER; R26ReYFP transgenics exposed to tamoxifen at different time points showed that the neurogenic potential of Sox10-expressing progenitors decreases progressively during embryogenesis and is undetectable at some point between P30 and P84. These findings raise the question of the origin of multilineage ENS progenitors isolated from cultures of post-neurogenic gut. To address whether such progenitors originate from Sox10-expressing glial cells, we cultured dissociated myenteric plexus of Sox10iCreER; R26ReYFP transgenics exposed to tamoxifen at p84. In such cultures, glial cells proliferate, and at least a subset of them can give rise to nNos, VIP and NPY neurons. Taken together, our data suggest that, although Sox10expressing cells in the ENS of adult animals loose their neurogenic capacity invivo, they can be activated to generate self renewing, multipotential progenitors.