Postnatal neural progenitors of the enteric nervous system are a potential source for future cell replacement therapies of developmental dysplasia like Hirschsprung's disease. However, little is known about the molecular mechanisms driving the homeostasis and differentiation of this cell pool. In this work, we conducted Affymetrix gene chip experiments to identify differences in gene regulation between proliferation and early differentiation of enteric neural progenitors. We detected a total of 1333 regulated genes that were linked to different groups of cellular mechanisms involved in cell cycle, apoptosis, neural proliferation, and differentiation. As expected, we found a strong inhibition of cell cycle progression as well as an enhanced expression of neuronal and glial markers. We further found a marked inactivation of the canonical Wnt pathway during the beginning of cellular differentiation. Taken together, this data illustrated the various mechanisms taking place during the proliferation and early differentiation of enteric neural progenitor cells.