GDNF/RET signaling increased Met and Etv5 mRNA in cultured ENS precursors, but MET protein immunoreactivity appeared normal in mice with Etv4 and Etv5 mutations. A, ENS precursors grown with 1 pg/ml GDNF had an eightfold increase in Etv5 mRNA, but not in Etv4 mRNA when compared with precursors cultured without GDNF. B, ENS precursors grown with 1 pg/ml GDNF also had a 230-fold increase in Met mRNA (N = 3 biological replicates). C–H, The myenteric plexus of adult Etv5M/M mice and P14 Etv4−/−; Etv5lacZ/WT compound mutants appeared grossly normal with no differences in MET-IR neuron density (N = 3 mice for each group). *p < 0.01 (Student's t test).