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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-...

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Detalles Bibliográficos
Autores principales: Landy, Mark A., Goyal, Megan, Casey, Katherine M., Liu, Chen, Lai, Helen C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
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.
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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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