A RET-ER81-NRG1 signaling pathway drives the development of pacinian corpuscles

Michael S. Fleming, Jian J. Li, Daniel Ramos, Tong Li, David A. Talmage, Abe Shin-Ichi Abe, Silvia Arber, Wenqin Luo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)10337-10355
Number of pages19
JournalJournal of Neuroscience
Volume36
Issue number40
DOIs
StatePublished - Oct 5 2016

Keywords

  • Development
  • ER81
  • Neuregulin 1
  • Neuron schwann cell interaction
  • Pacinian corpuscle
  • RET signaling

ASJC Scopus subject areas

  • Neuroscience(all)

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