title: Localization of immunoreactivity for deleted in colorectal cancer (DCC), the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents.
abstract: DCC (deleted in colorectal cancer)-the receptor of the netrin-1 neuronal guidance factor-is expressed and is active in the central nervous system (CNS) during development, but is down-regulated during maturation. The substantia nigra contains the highest level of netrin-1 mRNA in the adult rodent brain, and corresponding mRNA for DCC has also been detected in this region but has not been localized to any particular neuron type. In this study, an antibody raised against DCC was used to determine if the protein was expressed by adult dopamine neurons, and identify their distribution and projections. Significant DCC-immunoreactivity was detected in midbrain, where it was localized to ventrally displaced A9 dopamine neurons in the substantia nigra, and ventromedial A10 dopamine neurons predominantly situated in and around the interfascicular nucleus. Strong immunoreactivity was not detected in dopamine neurons found elsewhere, or in non-dopamine-containing neurons in the midbrain. Terminal fields selectively labeled with DCC antibody corresponded to known nigrostriatal projections to the dorsolateral striatal patches and dorsomedial shell of the accumbens, and were also detected in prefrontal cortex, septum, lateral habenular and ventral pallidum. The unique distribution of DCC-immunoreactivity in adult ventral midbrain dopamine neurons suggests that netrin-1/DCC signaling could function in plasticity and remodeling previously identified in dopamine projection pathways. In particular, a recent report that DCC is regulated through the ubiquitin-proteosome system via Siah/Sina proteins, is consistent with a potential involvement in genetic and sporadic forms of Parkinson's disease.
authors.affiliation: Prince of Wales Medical Research Institute, University of New South Wales, Barker Street Randwick, Sydney NSW 2031, Australia. p.osborne@usyd.edu.au
authors.forename: P B
authors.initials: PB
authors.lastname: Osborne
authors.forename: G M
authors.initials: GM
authors.lastname: Halliday
authors.forename: H M
authors.initials: HM
authors.lastname: Cooper
authors.forename: J R
authors.initials: JR
authors.lastname: Keast
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D064026:Calbindins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000075389:DCC Receptor; D004298:Dopamine / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D009434:Neural Pathways / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D017450:Receptors, Opioid, mu / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D064026:Calbindins; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D017450:Receptors, Opioid, mu; D064030:S100 Calcium Binding Protein G; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine