LOCALIZATION OF GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR-RECEPTOR-ALPHA AND C-RET MESSENGER-RNA IN RAT CENTRAL-NERVOUS-SYSTEM

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic f actor that influences the survival and function of several neuronal po pulations in the central (CNS) and peripheral nervous systems. The act ions of GDNF are mediated by a multicomponent receptor complex compose d of the tyrosine kinase product of c-ret and the ligand-binding prote in GDNF receptor alpha (GDNFR-alpha). In the present study, we used in situ hybridization to localize cells expressing the mRNA for these GD NF receptor subunits in rat CNS. As reported previously, GDNFR-alpha a nd c-ret mRNA are present in the substantia nigra and ventral tegmenta l area, regions containing GDNF-responsive dopamine neurons. However, both mRNA were found in motor neurons of spinal cord and brainstem nuc lei that innervate skeletal muscle. These areas include alpha motor ne urons in the ventral horn of spinal cord and neurons in hypoglossal, f acial, trigeminal, and abducens nuclei. In areas rostral to the substa ntia nigra, c-ret mRNA is not detected, whereas GDNFR-alpha is found i n numerous brain structures, including the hippocampus, cortex, medial geniculate, and the medial habenula, the latter area expressing the h ighest levels of GDNFR-alpha mRNA in brain. These results provide evid ence that c-ret and GDNFR-alpha mRNA are expressed in neuronal populat ions involved in motor function and provides further support for GDNF as a target-derived neurotrophic for these motor neurons. The observat ion that GDNFR-alpha mRNA is localized in several brain structures tha t do not contain detectable levels of c-ret mRNA indicates that either GDNFR-alpha utilizes signal transduction molecules other than c-ret i n these areas or that other GDNF-like ligands that utilize GDNFR-alpha as a receptor may be present. (C) 1998 Wiley-Liss, Inc.