Dickkopf1 induces enteric neurogenesis and gliogenesis in vitro if apoptosis is evaded

Neurogenesis in the postnatal enteric nervous system (ENS) is controversially discussed. Yet, deciphering the regenerative potential of the ENS is essential for our understanding and therapy of human enteric neuropathies. Dickkopf1 (DKK1) is a Wnt-antagonist and involved in the homeostasis of various tissues. We hypothesize that DKK1 could function as a negative regulator on the proliferation of ENS-progenitors in the postnatal gut of mice and human infants. Here, we provide evidence that DKK1 is expressed in the murine and human ENS. If applied to ENS-progenitors in vitro, DKK1 leads to an increased proliferation, however, followed by extensive apoptosis. Yet, once we block apoptosis, DKK1-stimulation markedly increases enteric neurogenesis in murine and human ENS-progenitors. Thus, DKK1 is a strong, ambivalent regulator of the ENS-progenitor cell pool in mice and humans. These results are fundamental steps to reshaping our understanding of the homeostasis of the ENS in health and disease.