The role of GDNF in patterning the excretory system

Dev Biol. 2005 Jul 1;283(1):70-84. doi: 10.1016/j.ydbio.2005.04.008.

Abstract

Mesenchymal-epithelial interactions are an important source of information for pattern formation during organogenesis. In the developing excretory system, one of the secreted mesenchymal factors thought to play a critical role in patterning the growth and branching of the epithelial ureteric bud is GDNF. We have tested the requirement for GDNF as a paracrine chemoattractive factor by altering its site of expression during excretory system development. Normally, GDNF is secreted by the metanephric mesenchyme and acts via receptors on the Wolffian duct and ureteric bud epithelium. Misexpression of GDNF in the Wolffian duct and ureteric buds resulted in formation of multiple, ectopic buds, which branched independently of the metanephric mesenchyme. This confirmed the ability of GDNF to induce ureter outgrowth and epithelial branching in vivo. However, in mutant mice lacking endogenous GDNF, kidney development was rescued to a substantial degree by GDNF supplied only by the Wolffian duct and ureteric bud. These results indicate that mesenchymal GDNF is not required as a chemoattractive factor to pattern the growth of the ureteric bud within the developing kidney, and that any positional information provided by the mesenchymal expression of GDNF may provide for renal branching morphogenesis is redundant with other signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning*
  • Gene Expression Regulation, Developmental*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Homeodomain Proteins / genetics*
  • In Situ Hybridization
  • Kidney / embryology*
  • Mesoderm / cytology
  • Mesoderm / physiology
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Restriction Mapping
  • Ureter / abnormalities
  • Ureter / embryology*

Substances

  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Homeodomain Proteins
  • Hoxb7 protein, mouse
  • Nerve Growth Factors