Differences and developmental changes in the responsiveness of PNS neurons to GDNF and neurturin.
We have studied the ability of GDNF and neurturin to promote the in vitro survival of populations of embryonic chicken parasympathetic, sympathetic, and sensory neurons. We show that these neurons are more responsive to one or other of these factors at particular stages of development. Whereas the parasympathetic neurons are more sensitive to neurturin at late embryonic stages, sympathetic neurons are more sensitive to neurturin at early stages. In contrast, sensory neurons of the nodose ganglion are more sensitive to GDNF throughout embryonic development. Using competitive RT/PCR, we measured the levels of mRNAs encoding GDNF and neurturin receptors in purified neurons. All neurons expressed Ret mRNA, which encodes the common receptor tyrosine kinase for GDNF and neurturin. Neurons that were more sensitive to GDNF expressed higher levels of GFRalpha-1 mRNA than GFRalpha-2 mRNA and neurons that were more sensitive to neurturin expressed higher levels of GFRalpha-2 mRNA than GFRalpha-1 mRNA. These results show that populations of PNS neurons differ markedly in their responsiveness to GDNF and neurturin at certain stages of the development and suggest that these differences are governed in part by the relative levels of expression of members of the GFRalpha family of GPI-linked receptors.
Forgie
A
A
Bute Medical Buildings, University of St. Andrews, St. Andrews, Fife, KY16 9AT, Scotland.
Doxakis
E
E
Buj-Bello
A
A
Wyatt
S
S
Davies
A M
AM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D051101:Neurturin; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D051101:Neurturin; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila