NEURTURIN AND GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR RECEPTOR-BETA (GDNFR-BETA), NOVEL PROTEINS RELATED TO GDNF AND GDNFR-ALPHA WITH SPECIFIC CELLULAR-PATTERNS OF EXPRESSION SUGGESTING ROLES IN THE DEVELOPING AND ADULT NERVOUS-SYSTEM AND IN PERIPHERAL ORGANS

Cloning strategies were used to identify a gene termed glial cell line -derived neurotrophic factor receptor-beta (GDNFR-beta) related to GDN FR-alpha. In situ hybridization was then used to map cellular expressi on of the GDNF-related trophic factor neurturin (NTN) and GDNFR-beta m RNA in developing and adult mice, and comparisons with GDNFR-alpha and RET were made. Neurturin is expressed in postnatal cerebral cortex, s triatum, several brainstem areas, and the pineal gland. GDNFR-beta mRN A was more widely expressed in the developing and adult CNS, including cerebral cortex, cerebellum, thalamus, zona incerta, hypothalamus, br ainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves. NTN colocalized with RET and GDNFR-alph a in ureteric buds of the developing kidney. The circular muscle layer of the developing intestines, smooth muscle of the urether, and devel oping bronchiolae also expressed NTN. GDNFR-beta was found in myenteri c but not submucosal intestinal plexuses. in developing salivary gland s NTN had an epithelial expression, whereas GDNFR-beta was expressed i n surrounding tissue. Neurturin and GDNFR-beta were present in develop ing sensory organs. In the gonads, NTN appeared to be expressed in Ser toli cells and in the epithelium of the oviduct, whereas GDNFR-beta wa s expressed by the germ cell line. Our findings suggest multiple roles for NTN and GDNFR-beta in the developing and adult organism. Although NTN and GDNFR-beta expression patterns are sometimes complementary, t his is not always the case, suggesting multiple modi operandi of GDNF and NTN in relation to RET and the two binding proteins, GDNFR-alpha a nd GDNFR-beta.