Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes
Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes
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 ofBdnfduring embryogenesis, but not postnatalBdnfdeletion orNtf3deletion, reproduced these results. Furthermore, prototypical SAI electrophysiological signatures were absent from skin regions whereBdnfwas 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.SIGNIFICANCE STATEMENTPeripheral 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.
- Children's Hospital of Pittsburgh United States
- University of Pittsburgh United States
- Case Western Reserve University United States
Mice, Knockout, Neurons, Brain-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-ret, Estrogen Antagonists, Embryonic Development, Cell Count, Mice, Transgenic, Merkel Cells, Mice, Tamoxifen, Pregnancy, Ganglia, Spinal, Basic Helix-Loop-Helix Transcription Factors, Animals, Receptor, trkB, Female, Receptor, trkC, Gene Deletion, Signal Transduction
Mice, Knockout, Neurons, Brain-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-ret, Estrogen Antagonists, Embryonic Development, Cell Count, Mice, Transgenic, Merkel Cells, Mice, Tamoxifen, Pregnancy, Ganglia, Spinal, Basic Helix-Loop-Helix Transcription Factors, Animals, Receptor, trkB, Female, Receptor, trkC, Gene Deletion, Signal Transduction
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