Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons

Neurturin (NTN) is a neuronal survival factor that activates the Ret tyrosi ne kinase in the presence of a GPI-linked coreceptor (either GFR alpha 1 or GFR alpha 2). Neurturin-deficient (NTN-/-) mice generated by homologous re combination are viable and fertile but have defects in the enteric nervous system, including reduced myenteric plexus innervation density and reduced gastrointestinal motility. Parasympathetic innervation of the lacrimal and submandibular salivary gland is dramatically reduced in NTN-/- mice, indica ting that Neurturin is a neurotrophic factor for parasympathetic neurons, G FR alpha 2-expressing cells in the trigeminal and dorsal root ganglia are a lso depleted in NTN-/- mice. The loss of GFR alpha 2-expressing neurons, in conjunction with earlier studies, provides strong support for GFR alpha 2/ Ret receptor complexes as the critical mediators of NTN function in vivo.