title: c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections.
abstract: Establishment of proper connectivity between peripheral sensory neurons and their central targets is required for an animal to sense and respond to various external stimuli. Dorsal root ganglion (DRG) neurons convey sensory signals of different modalities via their axon projections to distinct laminae in the dorsal horn of the spinal cord. In this study, we found that c-Maf was expressed predominantly in the interneurons of laminae III/IV, which primarily receive inputs from mechanoreceptive DRG neurons. In the DRG, c-Maf⁺ neurons also coexpressed neurofilament-200, a marker for the medium- and large-diameter myelinated afferents that transmit non-noxious information. Furthermore, mouse embryos deficient in c-Maf displayed abnormal development of dorsal horn laminae III/IV neurons, as revealed by the marked reduction in the expression of several marker genes for these neurons, including those for transcription factors MafA and Rora, GABA(A) receptor subunit α5, and neuropeptide cholecystokinin. In addition, among the four major subpopulations of DRG neurons marked by expression of TrkA, TrkB, TrkC, and MafA/GFRα2/Ret, c-Maf was required selectively for the proper differentiation of MafA⁺/Ret⁺/GFRα2⁺ low-threshold mechanoreceptors (LTMs). Last, we found that the central and peripheral projections of mechanoreceptive DRG neurons were compromised in c-Maf deletion mice. Together, our results indicate that c-Maf is required for the proper development of MafA⁺/Ret⁺/GFRα2⁺ LTMs in the DRG, their afferent projections in the dorsal horn and Pacinian corpuscles, as well as neurons in laminae III/IV of the spinal cord.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Tianwen
authors.initials: T
authors.lastname: Huang
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008465:Mechanoreceptors / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000378:metabolism; D010141:Pacinian Corpuscles / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000145:classification / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C485866:Barhl1 protein, mouse; D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; C496250:Gabra5 protein, mouse; D018398:Homeodomain Proteins; C491868:Lbx1h protein, mouse; D051473:Maf Transcription Factors, Large; C495608:Maf protein, mouse; C485160:Mafa protein, mouse; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D012097:Repressor Proteins; C539739:Rora protein, mouse; C487378:Tlx1 protein, mouse; C487377:Tlx3 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D002766:Cholecystokinin; D020917:Receptor, trkA