PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis.

Autor:	Bartesaghi L; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Wang Y; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Fontanet P; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Wanderoy S; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Berger F; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Wu H; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Akkuratova N; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden; Institute of Translational Biomedicine, Saint Petersburg State University, St. Petersburg, 199034, Russia., Bouçanova F; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Médard JJ; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Petitpré C; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden., Landy MA; Department of Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Zhang MD; Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, 17165, Sweden., Harrer P; Friedrich-Baur-Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Stendel C; Friedrich-Baur-Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Stucka R; Friedrich-Baur-Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Dusl M; Friedrich-Baur-Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Kastriti ME; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden; Center for Brain Research, Medical University Vienna, Vienna, Austria., Croci L; Center for Brain Research, Medical University Vienna, Vienna, Austria., Lai HC; Department of Neuroscience, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA., Consalez GG; Università Vita-Salute San Raffaele, 20132, Milan, Italy., Pattyn A; Institute for Neurosciences of Montpellier, INSERM, UMR1051, Hôpital Saint-Eloi, Montpellier, 34000, France., Ernfors P; Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, 17165, Sweden., Senderek J; Friedrich-Baur-Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Adameyko I; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 17165, Sweden; Center for Brain Research, Medical University Vienna, Vienna, Austria., Lallemend F; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden. Electronic address: francois.lallemend@ki.se., Hadjab S; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden. Electronic address: saida.hadjab@ki.se., Chrast R; Department of Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 17165, Sweden. Electronic address: roman.chrast@ki.se.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Mar 26; Vol. 26 (13), pp. 3484-3492.e4.
DOI:	10.1016/j.celrep.2019.02.098
Abstrakt:	The sensation of pain is essential for the preservation of the functional integrity of the body. However, the key molecular regulators necessary for the initiation of the development of pain-sensing neurons have remained largely unknown. Here, we report that, in mice, inactivation of the transcriptional regulator PRDM12, which is essential for pain perception in humans, results in a complete absence of the nociceptive lineage, while proprioceptive and touch-sensitive neurons remain. Mechanistically, our data reveal that PRDM12 is required for initiation of neurogenesis and activation of a cascade of downstream pro-neuronal transcription factors, including NEUROD1, BRN3A, and ISL1, in the nociceptive lineage while it represses alternative fates other than nociceptors in progenitor cells. Our results thus demonstrate that PRDM12 is necessary for the generation of the entire lineage of pain-initiating neurons. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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