title: GDNF and GFRalpha-1 are components of the axolotl pronephric duct guidance system.
abstract: In mammals, secretion of GDNF by the metanephrogenic mesenchyme is essential for branching morphogenesis of the ureteric bud and, thus, metanephric development. However, the expression pattern of GDNF and its receptor complex-the GPI-linked ligand-binding protein, GFRalpha-1, and the Ret tyrosine kinase signaling protein-indicates that it could operate at early steps in kidney development as well. Furthermore, the developing nephric systems of fish and amphibian embryos express components of the GDNF signaling system even though they do not make a metanephros. We provide evidence that GDNF signaling through GFRalpha-1 is sufficient to direct pathfinding of migrating pronephric duct cells in axolotl embryos by: (1) demonstrating that application of soluble GFRalpha-1 to an embryo lacking all GPI-linked proteins rescues PND migration in a dose-dependent fashion, (2) showing that application of excess soluble GFRalpha-1 to a normal embryo inhibits migration and that inhibition is dependent upon GDNF-binding activity, and (3) showing that the PND will migrate toward a GDNF-soaked bead in vivo, but will fail to migrate when GDNF is applied uniformly to the flank. These data suggest that PND pathfinding is accomplished by migration up a gradient of GDNF.
authors.affiliation: Department of Biology, Rider University, Lawrenceville, New Jersey, 08648, USA. drawbridge@rider.edu
authors.forename: J
authors.initials: J
authors.lastname: Drawbridge
authors.forename: C M
authors.initials: CM
authors.lastname: Meighan
authors.forename: E A
authors.initials: EA
authors.lastname: Mitchell
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology*; D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006651:Histocytochemistry; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D008845:Microinjections; D009024:Morphogenesis / Q000187:drug effects; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000494:pharmacology; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: 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; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase