GDNF and GFR alpha-1 are components of the axolotl pronephric duct guidance system

In mammals, secretion of GDNF by the metanephrogenic mesenchyme is essentia l for branching morphogenesis of the ureteric bud and, thus, metanephric de velopment. However, the expression pattern of GDNF and its receptor complex -the GPI-linked ligand-binding protein, GFR alpha -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 s ignaling through GFR alpha -1 is sufficient to direct pathfinding of migrat ing pronephric duct cells in axolotl embryos: by: (1) demonstrating that ap plication of soluble GFR alpha -1 to an embryo lacking all GPI-linked prote ins rescues PND migration in a dose-dependent fashion, (2) showing that app lication of excess soluble GFR alpha -1 to a normal embryo inhibits migrati on and that inhibition is dependent upon GDNF-binding activity, and (3) sho wing 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 sug gest that PND pathfinding is accomplished by migration up a gradient of GDN F. (C) 2000 Academic Press.