Defects in enteric innervation and kidney development in mice lacking GDNF

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) has been isolated as a neurotrophic factor for midbrain dopaminergic neurons(1). Because of its neurotrophic activity on a wide range of neuronal populations in vitro and in vivo(2-11), GDNF is being considered as a potential therapeutic agent for neuronal disorders(2,3,12). During mammalian development, it is expressed not only in the nervous system, but also very prominently in the metanephric kidney and the gastrointestinal tract, suggesting possible functions during organogenesis(7,11,13,14). We have investigated the role of GDNF during development by generating a null mutation in the murine GDNF locus, and found that mutant mice show kidney agenesis or dysgenesis and defective enteric innervation. We demonstrate that GDNF induces ureter bud formation and branching during metanephros development, and is essential for proper innervation of the gastrointestinal tract.