Differences and developmental changes in the responsiveness of PNS neuronsto GDNF and neurturin

We have studied the ability of GDNF and neurturin to promote the in vitro s urvival of populations of embryonic chicken parasympathetic, sympathetic, a nd sensory neurons. We show that these neurons are more responsive to one o r other of these factors at particular stages of development. Whereas the p arasympathetic neurons are more sensitive to neurturin at late embryonic st ages, sympathetic neurons are more sensitive to neurturin at early stages. In contrast, sensory neurons of the nodose ganglion are more sensitive to G DNF throughout embryonic development. Using competitive RT/PCR, we measured the levels of mRNAs encoding GDNF and neurturin receptors in purified neur ons. All neurons expressed net mRNA, which encodes the common receptor tyro sine kinase for GDNF and neurturin. Neurons that were more sensitive to GDN F expressed higher levels of GFR alpha-1 mRNA than GFR alpha-2 mRNA and neu rons that were more sensitive to neurturin expressed higher levels of GFR a lpha-2 mRNA than GFR alpha-1 mRNA. These results show that populations of P NS neurons differ markedly in their responsiveness to GDNF and neurturin at certain stages of the development and suggest that these differences are g overned in part by the relative levels of expression of members of the GFR alpha family of GPI-linked receptors.