title: Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes.
abstract: The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell-neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived Merkel cells. Transgenic mice lacking Merkel cells had normal dorsal root ganglion (DRG) neuron numbers, but fewer DRG neurons expressed the SAI markers TrkB, TrkC, and Ret. Merkel cell ablation also decreased downstream TrkB signaling in DRGs, and altered the expression of genes associated with SAI development and function. Skin- and Merkel cell-specific deletion of Bdnf during embryogenesis, but not postnatal Bdnf deletion or Ntf3 deletion, reproduced these results. Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions where Bdnf was deleted in embryonic Merkel cells. We conclude that BDNF produced by Merkel cells during a precise embryonic period guides SAI neuron development, providing the first direct evidence that the skin instructs sensory neuron molecular and functional maturation.
  
  
  CONCLUSIONS
  Peripheral sensory neurons show incredible phenotypic and functional diversity that is initiated early by cell-autonomous and local environmental factors found within the DRG. However, the contribution of target tissues to subsequent sensory neuron development remains unknown. We show that Merkel cells are required for the molecular and functional maturation of the SAI neurons that innervate them. We also show that this process is controlled by BDNF signaling. These findings provide new insights into the regulation of somatosensory neuron development and reveal a novel way in which Merkel cells participate in mechanosensation.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Erin G
authors.initials: EG
authors.lastname: Reed-Geaghan
authors.affiliation: Center for Neurosciences, and.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Wright
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: See
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adelman
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and.
authors.forename: Kuan Hsien
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, and.
authors.forename: H Richard
authors.initials: HR
authors.lastname: Koerber
authors.affiliation: Department of Pediatrics, Richard King Mellon Institute for Pediatric Research, University of Pittsburgh and Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224 stephen.maricich@chp.edu.
authors.forename: Stephen M
authors.identifier: http://orcid.org/0000-0001-8087-1954
authors.initials: SM
authors.lastname: Maricich
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002452:Cell Count; D047108:Embryonic Development; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D017353:Gene Deletion; D018862:Merkel Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D020813:Receptor, trkB / Q000502:physiology; D020812:Receptor, trkC / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019208:Brain-Derived Neurotrophic Factor; D004965:Estrogen Antagonists; D051096:Proto-Oncogene Proteins c-ret; D020813:Receptor, trkB; D020812:Receptor, trkC; D013629:Tamoxifen; C500943:Atoh1 protein, mouse; C494999:Ret protein, mouse
keywords: BDNF; Merkel cell; SAI; TrkB; mechanoreceptor