Maintenance of mammalian enteric nervous system progenitors by SOX10 and endothelin 3 signalling

Abstract

The transcriptional regulator SOX10 and the signalling molecule endothelin 3 have important roles in the development of the mammalian enteric nervous system (ENS). Using a clonal cell culture system, we show that SOX10 inhibits overt neuronal and glial differentiation of multilineage ENS progenitor cells(EPCs), without interfering with their neurogenic commitment. We also demonstrate that endothelin 3 inhibits reversibly the commitment and differentiation of EPCs along the neurogenic and gliogenic lineages,suggesting a role for this factor in the maintenance of multilineage ENS progenitors. Consistent with such a role, the proportion of Sox10-expressing progenitors in the total population of enteric neural crest cells is reduced in the gut of endothelin 3-deficient embryos. This reduction may be related to the requirement of endothelin signalling for the proliferation of ENS progenitors. The dependence of ENS progenitors on endothelin 3 is more pronounced at the migratory front of enteric neural crest cells, which is associated with relatively high levels of endothelin 3 mRNA. Our findings indicate that SOX10 and endothelin 3 have a crucial role in the maintenance of multilineage enteric nervous system progenitors.