p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling
Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly understood. Here, we show that the p75 neurotr...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717313128 |
| _version_ | 1828383146940301312 |
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| author | Zhijiang Chen Christopher R. Donnelly Bertha Dominguez Yoshinobu Harada Weichun Lin Alan S. Halim Tasha G. Bengoechea Brian A. Pierchala Kuo-Fen Lee |
| author_facet | Zhijiang Chen Christopher R. Donnelly Bertha Dominguez Yoshinobu Harada Weichun Lin Alan S. Halim Tasha G. Bengoechea Brian A. Pierchala Kuo-Fen Lee |
| author_sort | Zhijiang Chen |
| collection | DOAJ |
| description | Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly understood. Here, we show that the p75 neurotrophin receptor interacts with Ret and its GFRα co-receptor upon stimulation with glial cell line-derived neurotrophic factor (GDNF). Furthermore, we demonstrate that p75 is required for GDNF-mediated Ret activation, survival, and cell surface localization of Ret in DRG neurons. In mice in which p75 is deleted specifically within sensory neurons beginning at E12.5, we observe that approximately 20% of neurons are lost between P14 and adulthood, and these losses selectively occur within a subpopulation of Ret+ nonpeptidergic nociceptors, with neurons expressing low levels of Ret impacted most heavily. These results suggest that p75 is required for the development of the nonpeptidergic nociceptor lineage by fine-tuning Ret-mediated trophic support. |
| first_indexed | 2024-12-10T04:43:38Z |
| format | Article |
| id | doaj.art-f54fc2fdffb44db285f2c470ec1ed85d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T04:43:38Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f54fc2fdffb44db285f2c470ec1ed85d2022-12-22T02:01:49ZengElsevierCell Reports2211-12472017-10-0121370772010.1016/j.celrep.2017.09.037p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret SignalingZhijiang Chen0Christopher R. Donnelly1Bertha Dominguez2Yoshinobu Harada3Weichun Lin4Alan S. Halim5Tasha G. Bengoechea6Brian A. Pierchala7Kuo-Fen Lee8The Salk Institute, Peptide Biology Laboratories, La Jolla, CA 92037, USADepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USAThe Salk Institute, Peptide Biology Laboratories, La Jolla, CA 92037, USAThe Salk Institute, Peptide Biology Laboratories, La Jolla, CA 92037, USAUT Southwestern Medical Center, Neuroscience, Dallas, TX 75390, USADepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USAThe Salk Institute, Peptide Biology Laboratories, La Jolla, CA 92037, USADepartment of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USAThe Salk Institute, Peptide Biology Laboratories, La Jolla, CA 92037, USAProducing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly understood. Here, we show that the p75 neurotrophin receptor interacts with Ret and its GFRα co-receptor upon stimulation with glial cell line-derived neurotrophic factor (GDNF). Furthermore, we demonstrate that p75 is required for GDNF-mediated Ret activation, survival, and cell surface localization of Ret in DRG neurons. In mice in which p75 is deleted specifically within sensory neurons beginning at E12.5, we observe that approximately 20% of neurons are lost between P14 and adulthood, and these losses selectively occur within a subpopulation of Ret+ nonpeptidergic nociceptors, with neurons expressing low levels of Ret impacted most heavily. These results suggest that p75 is required for the development of the nonpeptidergic nociceptor lineage by fine-tuning Ret-mediated trophic support.http://www.sciencedirect.com/science/article/pii/S2211124717313128p75RetGDNFdorsal root ganglionnonpeptidergicnociceptive neuron |
| spellingShingle | Zhijiang Chen Christopher R. Donnelly Bertha Dominguez Yoshinobu Harada Weichun Lin Alan S. Halim Tasha G. Bengoechea Brian A. Pierchala Kuo-Fen Lee p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling Cell Reports p75 Ret GDNF dorsal root ganglion nonpeptidergic nociceptive neuron |
| title | p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling |
| title_full | p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling |
| title_fullStr | p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling |
| title_full_unstemmed | p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling |
| title_short | p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling |
| title_sort | p75 is required for the establishment of postnatal sensory neuron diversity by potentiating ret signaling |
| topic | p75 Ret GDNF dorsal root ganglion nonpeptidergic nociceptive neuron |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717313128 |
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