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Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation
Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue-...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048104/ https://www.ncbi.nlm.nih.gov/pubmed/33789102 http://dx.doi.org/10.1016/j.celrep.2021.108913 |
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author | Landy, Mark A. Goyal, Megan Casey, Katherine M. Liu, Chen Lai, Helen C. |
author_facet | Landy, Mark A. Goyal, Megan Casey, Katherine M. Liu, Chen Lai, Helen C. |
author_sort | Landy, Mark A. |
collection | PubMed |
description | Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that, in adult DRGs, Prdm12 is dispensable for most pain-sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we find mostly unique changes in adult Prdm12 knockout DRGs compared with embryonic knockout and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time. |
format | Online Article Text |
id | pubmed-8048104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-80481042021-04-15 Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation Landy, Mark A. Goyal, Megan Casey, Katherine M. Liu, Chen Lai, Helen C. Cell Rep Article Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that, in adult DRGs, Prdm12 is dispensable for most pain-sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we find mostly unique changes in adult Prdm12 knockout DRGs compared with embryonic knockout and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time. 2021-03-30 /pmc/articles/PMC8048104/ /pubmed/33789102 http://dx.doi.org/10.1016/j.celrep.2021.108913 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Landy, Mark A. Goyal, Megan Casey, Katherine M. Liu, Chen Lai, Helen C. Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title | Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title_full | Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title_fullStr | Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title_full_unstemmed | Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title_short | Loss of Prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
title_sort | loss of prdm12 during development, but not in mature nociceptors, causes defects in pain sensation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048104/ https://www.ncbi.nlm.nih.gov/pubmed/33789102 http://dx.doi.org/10.1016/j.celrep.2021.108913 |
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