title: A RET-ER81-NRG1 Signaling Pathway Drives the Development of Pacinian Corpuscles.
abstract: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET+mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression. Interestingly, Er81 mutants have normal myelination but exhibit deficient interactions between axons and corpuscle-forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not required for communication with myelinating Schwann cells is specifically decreased in Er81-null somatosensory neurons. Collectively, our results suggest that a RET-ER81-NRG1 signaling pathway promotes axon communication with nonmyelinating Schwann cells, and that neurons use distinct mechanisms to interact with different types of Schwann cells.
  
  
  
  Communication between neurons and Schwann cells is critical for development, normal function, and regeneration of the peripheral nervous system. Despite many studies about axonal communication with myelinating Schwann cells, mostly via a specific isoform of Neuregulin1, the molecular nature of axonal communication with nonmyelinating Schwann cells is poorly understood. Here, we described a RET-ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ nonmyelinating Schwann cells. We also showed that this signaling pathway uses isoforms of Neuregulin1 that are not involved in myelination, providing evidence that neurons use different isoforms of Neuregulin1 to interact with different types of Schwann cells.
authors.affiliation: Department of Neuroscience and.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Fleming
authors.affiliation: Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.
authors.forename: Jian J
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Neuroscience and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramos
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794.
authors.forename: David A
authors.identifier: 0000-0003-4627-3007
authors.initials: DA
authors.lastname: Talmage
authors.affiliation: Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan, and.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Abe
authors.affiliation: Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland and Friedrich Miescher Institute, 4058 Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arber
authors.affiliation: Department of Neuroscience and luow@mail.med.upenn.edu.
authors.forename: Wenqin
authors.identifier: 0000-0002-2486-807X
authors.initials: W
authors.lastname: Luo
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010141:Pacinian Corpuscles / Q000254:growth & development* / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C490641:Etv1 protein, mouse; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse
keywords: ER81; Pacinian corpuscle; RET signaling; development; neuregulin 1; neuron Schwann cell interaction