DEFECTS IN ENTERIC INNERVATION AND KIDNEY DEVELOPMENT IN MICE LACKINGGDNF

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) has been isolated a s a neurotrophic factor for midbrain dopaminergic neurons(1). Because of its neurotrophic activity on a wide range of neuronal populations i n vitro and in vivo(2-11), GDNF is being considered as a potential the rapeutic agent for neuronal disorders(2,3,12). During mammalian develo pment, it is expressed not only in the nervous system, but also very p rominently in the metanephric kidney and the gastrointestinal tract, s uggesting 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 ki dney agenesis or dysgenesis and defective enteric innervation. We demo nstrate that GDNF induces ureter bud formation and branching during me tanephros development, and is essential for proper innervation of the gastrointestinal tract.