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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Different developmental patterns of melanocortin MC3 and MC4 receptor mRNA: predominance of Mc4 in fetal rat nervous system.

Melanocortins are thought to be involved in neuronal development and regeneration. Pro-opiomelanocortin (POMC), the precursor of alpha-melanocyte stimulating hormone (alpha-MSH), gamma-MSH, ACTH, and beta-endorphin, becomes detectable in rat hypothalamic neurons from gestational day (E) 12. 5. We recently described stage- and region-specific ontogenetic patterns of binding sites for the alpha-MSH analogue [125I]-Nle4,D-Phe7-alpha-MSH ([125I]-NDP), with the first localizations in epithalamus and sympathetic chain at E13. [125I]-NDP binds to all known melanocortin receptors, including MC3-R and MC4-R, the predominant melanocortin receptors in nervous system. To identify the receptor type expressed during ontogeny, the developmental pattern of MC3-R and MC4-R mRNA was investigated by in situ hybridization in fetuses and offspring of time-pregnant Long Evans rats between E14 and postnatal day (P) 27. MC4-R mRNA was found to be the predominant species during the entire fetal period. It was localized in all fetal areas exhibiting distinct [125I]-NDP binding, starting with sympathetic ganglia and epithalamus (E14), and including sensory trigeminal nuclei ( E16), dorsal motor nucleus of vagus ( E16) and cranial nerve ganglia, inferior olive (E18) and cerebellum (E18), striatal regions ( E16), and entorhinal cortex (E22). In contrast, MC3-R mRNA was detectable only in the postnatal period, with a fast increase in expression in the ventromedial and arcuate nuclei. The early presence of MC4-R mRNA in central and peripheral nervous system and transient regional peaks of mRNA expression, often concomitant with periods of neural network formation, suggest a role of this receptor type in early ontogeny. The MC3 receptor may be involved in analogous processes during postnatal development.[1]


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