Development of cranial parasympathetic ganglia requires sequential actions of GDNF and neurturin.
The neurotrophic factors that influence the development and function of the parasympathetic branch of the autonomic nervous system are obscure. Recently, neurturin has been found to provide trophic support to neurons of the cranial parasympathetic ganglion. Here we show that GDNF signaling via the RET/GFR(alpha)1 complex is crucial for the development of cranial parasympathetic ganglia including the submandibular, sphenopalatine and otic ganglia. GDNF is required early for proliferation and/or migration of the neuronal precursors for the sphenopalatine and otic ganglia. Neurturin exerts its effect later and is required for further development and maintenance of these neurons. This switch in ligand dependency during development is at least partly governed by the altered expression of GFR(&agr;) receptors, as evidenced by the predominant expression of GFR(&agr;)2 in these neurons after ganglion formation.
Enomoto
H
H
Department of Pathology and Internal Medicine, Washington University School of Medicine, Box 8118, St Louis, MO 63110, USA.
Heuckeroth
R O
RO
Golden
J P
JP
Johnson
E M
EM
Milbrandt
J
J
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins; D017615:Enteric Nervous System / Q000196:embryology; D005726:Ganglia, Parasympathetic / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
D017931:DNA Primers; D029721:Drosophila Proteins; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse