In any event, the conceptual conclusion that Edn3-Ednrb signaling converges on GDNF-Ret function in both the Pax2Cre and Wnt1Cre lineages is supported by both the in vitro and in vivo observations and helps to explain the common phenotype of Hirschsprung disease that is seen when any component is mutated. Here, GDNF is linked to Hirschsprung disease.