Expression of neurturin, GDNF, and their receptors in the adult mouse CNS.
Neurturin (NTN) and glial cell line-derived neurotrophic factor (GDNF) are the first two members of the GDNF family (GF) of neurotrophic factors. These two proteins are potent survival factors for several populations of central and peripheral neurons in mature and developing rodents. The receptor for these factors is a multicomponent complex that includes the RET (rearranged during transfection) tyrosine kinase receptor and one of two glycosyl phosphatidylinositol (GPI)-linked ligand-binding components called GDNF family receptor alphas (GFRalpha-1 and GFRalpha-2). We have used in situ hybridization to study the mRNA expression of NTN, GDNF, RET, GFRalpha-1, and GFRalpha-2 in the central nervous system (CNS) of adult mice. GF receptors are expressed in several areas in which neuronal populations known to respond to NTN and GDNF are located, including the ventral horn of the spinal cord and the compacta region of the substantia nigra. In addition, we have demonstrated receptor expression in other areas of the brain including the thalamus and hypothalamus. Neurons in these areas express GF receptors, and therefore, may respond to NTN or GDNF. NTN and GDNF are expressed in targets of neurons that express GF receptors. The pattern of GF factor and receptor expression in the adult brain suggests a role for these factors in maintaining neuronal circuits in the mature CNS.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. jgolden@pharmdec.wustl.edu
J P
JP
Golden
R H
RH
Baloh
P T
PT
Kotzbauer
P A
PA
Lampe
P A
PA
Osborne
J
J
Milbrandt
E M
EM
Johnson
D000367:Age Factors; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D001933:Brain Stem / Q000737:chemistry / Q000166:cytology; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology; D029721:Drosophila Proteins; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007031:Hypothalamus / Q000737:chemistry / Q000166:cytology; D017403:In Situ Hybridization; D008636:Mesencephalon / Q000737:chemistry / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR / Q000502:physiology*; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents / Q000378:metabolism*; D051101:Neurturin; D009830:Olfactory Bulb / Q000737:chemistry / Q000166:cytology; D016548:Prosencephalon / Q000737:chemistry / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology; D013788:Thalamus / Q000737:chemistry / Q000166:cytology
D029721:Drosophila Proteins; C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D051101:Neurturin; C495056:Nrtn protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse