title: Age-dependent differences in the effects of GDNF and NT-3 on the development of neurons and glia from neural crest-derived precursors immunoselected from the fetal rat gut: expression of GFRalpha-1 in vitro and in vivo.
abstract: No enteric neurons or glia develop in the gut below the rostral foregut in mice lacking glial cell line-derived neurotrophic factor (GDNF) or Ret. We analyzed the nature and age dependence of the effects of GDNF and, for comparison, those of NT-3, on the in vitro development of the precursors of enteric neurons and glia. Positive and negative immunoselection with antibodies to p75(NTR) were used to isolate crest-derived and crest-depleted populations of cells from the fetal rat bowel at E12, 14, and 16. Cells were typed immunocytochemically. GDNF stimulated the proliferation of nestin-expressing precursor cells isolated at E12, but not at E14-16. GDNF promoted the development of peripherin-expressing neurons (E12 >> E14-16) and expression of TrkC. GDNF inhibited expression of S-100-expressing glia at E14-16. NT-3 did not affect cells isolated at E12, never stimulated precursors to proliferate, and promoted glial as well as neuronal development at E14-16. GFRalpha-1 was expressed both by crest- and non-crest-derived cells, although only crest-derived cells anchored GFRalpha-1 and GFRalpha-2 (GFRalpha-1 >> GFRalpha-2). GDNF increased the number of neurons anchoring GFRalpha-1. GFRalpha-1 is immunocytochemically detectable in neurons of the E13 intestine and persists in adult neurons of both plexuses. We suggest that GDNF stimulates the proliferation of an early (E12) NT-3-insensitive precursor common to enteric neurons and glia; by E14, this common precursor is replaced by specified NT-3-responsive neuronal and glial progenitors. GDNF exerts a neurotrophic, but not a mitogenic, effect on the neuronal progenitor. The glial progenitor is not maintained by GDNF.
authors.affiliation: Department of Anatomy and Cell Biology,Columbia University, College of Physicians and Surgeons, New York, New York, 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chalazonitis
authors.forename: T P
authors.initials: TP
authors.lastname: Rothman
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: M D
authors.initials: MD
authors.lastname: Gershon
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development; D017615:Enteric Nervous System / Q000196:embryology* / Q000502:physiology; D005865:Gestational Age; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; C494988:Gfra1 protein, mouse; C494989:Gfra1 protein, rat; C494992:Gfra2 protein, rat; 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; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C495001:Ret protein, rat