Dhh is expressed in SCPs that invade the gut and generate enteric neurons even in the absence of Ret signaling.15 It was also shown that the SCs residing in the extrinsic nerves in mouse models of HSCR can be activated by a reduction in the intrinsic neurons21 or rectal administration of GDNF.16 Soret et al.16 gave rectal GDNF enemas to early postnatal HSCR mice and found induction of neurogenesis from Sox10+ SCs residing in the extrinsic fibers, reversing the aganglionic phenotype and improving colonic motility and survival. The gene discussed is GDNF; the disease is Hirschsprung disease.