Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA
Summary: In humans, many cases of congenital insensitivity to pain (CIP) are caused by mutations of components of the NGF/TrkA signaling pathway, which is required for survival and specification of nociceptors and plays a major role in pain processing. Mutations in PRDM12 have been identified in CIP...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719302839 |
| _version_ | 1818262984292564992 |
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| author | Simon Desiderio Simon Vermeiren Claude Van Campenhout Sadia Kricha Elisa Malki Sven Richts Emily V. Fletcher Thomas Vanwelden Bela Z. Schmidt Kristine A. Henningfeld Tomas Pieler C. Geoffrey Woods Vanja Nagy Catherine Verfaillie Eric J. Bellefroid |
| author_facet | Simon Desiderio Simon Vermeiren Claude Van Campenhout Sadia Kricha Elisa Malki Sven Richts Emily V. Fletcher Thomas Vanwelden Bela Z. Schmidt Kristine A. Henningfeld Tomas Pieler C. Geoffrey Woods Vanja Nagy Catherine Verfaillie Eric J. Bellefroid |
| author_sort | Simon Desiderio |
| collection | DOAJ |
| description | Summary: In humans, many cases of congenital insensitivity to pain (CIP) are caused by mutations of components of the NGF/TrkA signaling pathway, which is required for survival and specification of nociceptors and plays a major role in pain processing. Mutations in PRDM12 have been identified in CIP patients that indicate a putative role for this transcriptional regulator in pain sensing. Here, we show that Prdm12 expression is restricted to developing and adult nociceptors and that its genetic ablation compromises their viability and maturation. Mechanistically, we find that Prdm12 is required for the initiation and maintenance of the expression of TrkA by acting as a modulator of Neurogenin1/2 transcription factor activity, in frogs, mice, and humans. Altogether, our results identify Prdm12 as an evolutionarily conserved key regulator of nociceptor specification and as an actionable target for new pain therapeutics. : Desiderio et al. report that, in developing somatosensory neurons, Prdm12 is restricted to the nociceptors and that these are selectively eliminated from Prdm12 mutant mice. In Xenopus and human iPSCs, they show that Prdm12, in conjunction with bHLH proneural proteins, promotes the expression of the neurotrophin receptor TrkA. Keywords: zinc-finger transcription factor, neurotrophic receptor, nociceptors, pain, cell fate specification, mouse, Xenopus, stem cells |
| first_indexed | 2024-12-12T19:11:48Z |
| format | Article |
| id | doaj.art-fae861bc85d64815aed45ce1e14b0c6b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T19:11:48Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fae861bc85d64815aed45ce1e14b0c6b2022-12-22T00:14:50ZengElsevierCell Reports2211-12472019-03-01261335223536.e5Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkASimon Desiderio0Simon Vermeiren1Claude Van Campenhout2Sadia Kricha3Elisa Malki4Sven Richts5Emily V. Fletcher6Thomas Vanwelden7Bela Z. Schmidt8Kristine A. Henningfeld9Tomas Pieler10C. Geoffrey Woods11Vanja Nagy12Catherine Verfaillie13Eric J. Bellefroid14ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, BelgiumULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, BelgiumULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, BelgiumULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, BelgiumULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium; KU Leuven, Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, 3000 Leuven, BelgiumInstitute of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Goettingen, 37077 Goettingen, GermanyCambridge Institute for Medical Research, University of Cambridge, CB2 0QQ Cambridge, UKKU Leuven, Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, 3000 Leuven, BelgiumKU Leuven, Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, 3000 Leuven, BelgiumInstitute of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Goettingen, 37077 Goettingen, GermanyInstitute of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Goettingen, 37077 Goettingen, GermanyCambridge Institute for Medical Research, University of Cambridge, CB2 0QQ Cambridge, UK; Department of Medical Genetics, University of Cambridge, CB2 0XY Cambridge, UKInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, 1090 Vienna, AustriaKU Leuven, Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, 3000 Leuven, BelgiumULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium; Corresponding authorSummary: In humans, many cases of congenital insensitivity to pain (CIP) are caused by mutations of components of the NGF/TrkA signaling pathway, which is required for survival and specification of nociceptors and plays a major role in pain processing. Mutations in PRDM12 have been identified in CIP patients that indicate a putative role for this transcriptional regulator in pain sensing. Here, we show that Prdm12 expression is restricted to developing and adult nociceptors and that its genetic ablation compromises their viability and maturation. Mechanistically, we find that Prdm12 is required for the initiation and maintenance of the expression of TrkA by acting as a modulator of Neurogenin1/2 transcription factor activity, in frogs, mice, and humans. Altogether, our results identify Prdm12 as an evolutionarily conserved key regulator of nociceptor specification and as an actionable target for new pain therapeutics. : Desiderio et al. report that, in developing somatosensory neurons, Prdm12 is restricted to the nociceptors and that these are selectively eliminated from Prdm12 mutant mice. In Xenopus and human iPSCs, they show that Prdm12, in conjunction with bHLH proneural proteins, promotes the expression of the neurotrophin receptor TrkA. Keywords: zinc-finger transcription factor, neurotrophic receptor, nociceptors, pain, cell fate specification, mouse, Xenopus, stem cellshttp://www.sciencedirect.com/science/article/pii/S2211124719302839 |
| spellingShingle | Simon Desiderio Simon Vermeiren Claude Van Campenhout Sadia Kricha Elisa Malki Sven Richts Emily V. Fletcher Thomas Vanwelden Bela Z. Schmidt Kristine A. Henningfeld Tomas Pieler C. Geoffrey Woods Vanja Nagy Catherine Verfaillie Eric J. Bellefroid Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA Cell Reports |
| title | Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA |
| title_full | Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA |
| title_fullStr | Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA |
| title_full_unstemmed | Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA |
| title_short | Prdm12 Directs Nociceptive Sensory Neuron Development by Regulating the Expression of the NGF Receptor TrkA |
| title_sort | prdm12 directs nociceptive sensory neuron development by regulating the expression of the ngf receptor trka |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719302839 |
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