Neurturin: An autocrine regulator of renal collecting duct development

Urine is produced in the kidney by excretory nephrons and is drained a tree -like system of collecting ducts to the ureter. collecting ducts develop by arborisation of an initially unbranched epithelial rudiment, the ureteric bud, which ramifies through the surrounding mesenchyme and induces the form ation of nephrons by mesenchyme-to-epithelial transition. The question of h ow collecting duct morphogenesis is controlled is on important one, from th e points of view of both basic developmental biology and congenital renal p athology (multi- and polycystic renal disease, and some forms of renal agen esis, arise from defective collecting duct development). We report that neu rturin, a neurotrophin related to glial cell line-derived neurotrophic fact or and expressed in the developing kidney, acts as a collecting duct morpho gen in culture. Applied in culture medium, ii promotes epithelial branching and can induce branch initiation that has otherwise been blocked by deplet ing cultured kidneys of their sulfated proteoglycans or by antibody treatme nts. Applied locally on agarose beads, neurturin induces supernumerary uret eric buds to emerge from the wolffian duct and causes nearby collecting duc t branches to distend to an abnormally large diameter. Like iis receptors, neurturin is expressedby the developing collecting ducts themselves, sugges ting that ii forms an autocrine morphoregulatory control loop. This is in m arked contrast to previously identified morphogens such as glial cell line derived neurotrophic factor and hepatocyte growth factor, which act in a pa racrine manner. (C) 1999 Wiley-Liss Inc.