The study reveals four important findings: (1) mRNA expression of GDNF and its receptors GFRα1 and RET is down-regulated in the muscularis propria of patients with DD; (2) the main source of GDNF is the intestinal smooth muscle, while RET is mainly expressed in enteric ganglia in which GFRα1 is also found; (3) GDNF up-regulates its corresponding receptors in enteric nerve cell cultures; (4) GDNF treatment promotes neuronal differentiation and plasticity of enteric nerve cell cultures. This evidence concerns the gene GFRA1 and dentin dysplasia.