@article{70b1b8374b9c4c1e9429c6d177a21741,
title = "PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis",
abstract = "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. The sensation of pain, temperature, and itch by neurons of the nociceptive lineage is essential for animal survival. Bartesaghi et al. report that the transcriptional regulator PRDM12 is indispensable in neural crest cells (NCCs) for the initiation of the sensory neuronal differentiation program that generates the entire nociceptive lineage.",
keywords = "Prdm12, neural crest cells, neurogenesis, nociceptive neurons, pain",
author = "Luca Bartesaghi and Yiqiao Wang and Paula Fontanet and Simone Wanderoy and Finja Berger and Haohao Wu and Natalia Akkuratova and Filipa Bou{\c c}anova and M{\'e}dard, {Jean Jacques} and Charles Petitpr{\'e} and Landy, {Mark A.} and Zhang, {Ming Dong} and Philip Harrer and Claudia Stendel and Rolf Stucka and Marina Dusl and Kastriti, {Maria Eleni} and Laura Croci and Lai, {Helen C.} and Consalez, {Gian Giacomo} and Alexandre Pattyn and Patrik Ernfors and Jan Senderek and Igor Adameyko and Francois Lallemend and Saida Hadjab and Roman Chrast",
note = "Funding Information: We thank Prof. Frances Lefcort for anti-chicken TRKA and TRKC antibodies, Prof. Tomas H{\"o}kfelt for anti-rabbit CGRP antibody, Prof. Francois Guillemot for the Ngn-null mice, the CLICK Imaging Facility supported by the Knut and Alice Wallenberg Foundation, and Prof. Yiochi Shinkai for the pCAG-FLAG-mPRDM12 plasmid. This work was supported by grants from StratNeuro, the Swedish Research Council, and KID funding (F.L. and R.C.); the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the Swedish Brain Foundation, the {\AA}ke Wiberg Foundation, Karolinska Institutet (Faculty Funded Career Position), the Ragnar S{\"o}derberg Foundation (Ragnar S{\"o}derberg Fellow in Medicine), and a Ming Wai Lau research grant (F.L.); ERC AdvPainCells 740491 and the Knut and Alice Wallenberg Foundation (P.E.); Inserm (A.P.); the Rita Allen Foundation (H.C.L.); the Russian Science Foundation (grant 16-15-10273 to N.A.); the German Federal Ministry of Education and Research (BMBF) through the German Network for Charcot-Marie-Tooth Neuropathies (CMT-NET) (01GM1511B to J.S.); and Fritz-Thyssen-Stiftung (Az. 10.15.1.021MN to J.S. and C.S.) and the LMU FoeFoLe program (36/2014 to J.S.). Funding Information: We thank Prof. Frances Lefcort for anti-chicken TRKA and TRKC antibodies, Prof. Tomas H{\"o}kfelt for anti-rabbit CGRP antibody, Prof. Francois Guillemot for the Ngn-null mice, the CLICK Imaging Facility supported by the Knut and Alice Wallenberg Foundation , and Prof. Yiochi Shinkai for the pCAG-FLAG-mPRDM12 plasmid. This work was supported by grants from StratNeuro , the Swedish Research Council , and KID funding (F.L. and R.C.); the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the Swedish Brain Foundation , the {\AA}ke Wiberg Foundation , Karolinska Institutet (Faculty Funded Career Position), the Ragnar S{\"o}derberg Foundation (Ragnar S{\"o}derberg Fellow in Medicine), and a Ming Wai Lau research grant (F.L.); ERC AdvPainCells 740491 and the Knut and Alice Wallenberg Foundation (P.E.); Inserm (A.P.); the Rita Allen Foundation (H.C.L.); the Russian Science Foundation (grant 16-15-10273 to N.A.); the German Federal Ministry of Education and Research (BMBF) through the German Network for Charcot-Marie-Tooth Neuropathies (CMT-NET) ( 01GM1511B to J.S.); and Fritz-Thyssen-Stiftung ( Az. 10.15.1.021MN to J.S. and C.S.) and the LMU FoeFoLe program ( 36/2014 to J.S.). Funding Information: We thank Prof. Frances Lefcort for anti-chicken TRKA and TRKC antibodies, Prof. Tomas H?kfelt for anti-rabbit CGRP antibody, Prof. Francois Guillemot for the Ngn-null mice, the CLICK Imaging Facility supported by the Knut and Alice Wallenberg Foundation, and Prof. Yiochi Shinkai for the pCAG-FLAG-mPRDM12 plasmid. This work was supported by grants from StratNeuro, the Swedish Research Council, and KID funding (F.L. and R.C.); the Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), the Swedish Brain Foundation, the ?ke Wiberg Foundation, Karolinska Institutet (Faculty Funded Career Position), the Ragnar S?derberg Foundation (Ragnar S?derberg Fellow in Medicine), and a Ming Wai Lau research grant (F.L.); ERC AdvPainCells 740491 and the Knut and Alice Wallenberg Foundation (P.E.); Inserm (A.P.); the Rita Allen Foundation (H.C.L.); the Russian Science Foundation (grant 16-15-10273 to N.A.); the German Federal Ministry of Education and Research (BMBF) through the German Network for Charcot-Marie-Tooth Neuropathies (CMT-NET) (01GM1511B to J.S.); and Fritz-Thyssen-Stiftung (Az. 10.15.1.021MN to J.S. and C.S.) and the LMU FoeFoLe program (36/2014 to J.S.). F.L. S.H. and R.C. contributed equally, and each has the right to list her or himself last in bibliographic documents. L.B. and Y.W. contributed equally, and each has the right to list himself first in bibliographic documents. F.L. S.H. and R.C. designed and supervised the study. L.B. and Y.W. performed most experiments. R.S. C.S. P.H. M.D. and J.S. generated Prdm12? and Prdm12LZ alleles. P.F. S.W. F. Berger, H.W. C.P. N.A. F. Bou?anova, J.-J.M. M.-D.Z. and S.H. performed some immunostaining experiments and microscopy analysis. M.A.L. M.E.K. H.C.L. A.P. J.-J.M. P.E. L.C. G.G.C. and I.A. processed and provided mouse tissues for analysis. N.A. performed chicken electroporation. F.L. S.H. and R.C. prepared the figures. F.L. S.H. and R.C. wrote the paper with input from all other authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = mar,
day = "26",
doi = "10.1016/j.celrep.2019.02.098",
language = "English (US)",
volume = "26",
pages = "3484--3492.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}