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

Luca Bartesaghi; Yiqiao Wang; Paula Fontanet; Simone Wanderoy; Finja Berger; Haohao Wu; Natalia Akkuratova; Filipa Bouçanova; Jean Jacques Médard; Charles Petitpré; Mark A. Landy; Ming Dong Zhang; Philip Harrer; Claudia Stendel; Rolf Stucka; Marina Dusl; Maria Eleni Kastriti; Laura Croci; Helen C. Lai; Gian Giacomo Consalez; Alexandre Pattyn; Patrik Ernfors; Jan Senderek; Igor Adameyko; Francois Lallemend; Saida Hadjab; Roman Chrast

doi:10.1016/j.celrep.2019.02.098

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

Luca Bartesaghi, Yiqiao Wang, Paula Fontanet, Simone Wanderoy, Finja Berger, Haohao Wu, Natalia Akkuratova, Filipa Bouçanova, Jean Jacques Médard, Charles Petitpré, Mark A. Landy, Ming Dong Zhang, Philip Harrer, Claudia Stendel, Rolf Stucka, Marina Dusl, Maria Eleni Kastriti, Laura Croci, Helen C. Lai, Gian Giacomo ConsalezAlexandre Pattyn, Patrik Ernfors, Jan Senderek, Igor Adameyko, Francois Lallemend, Saida Hadjab, Roman Chrast

Neuroscience

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3484-3492.e4
Journal	Cell Reports
Volume	26
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2019.02.098
State	Published - Mar 26 2019

Keywords

Prdm12
neural crest cells
neurogenesis
nociceptive neurons
pain

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2019.02.098

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Bartesaghi, L., Wang, Y., Fontanet, P., Wanderoy, S., Berger, F., Wu, H., Akkuratova, N., Bouçanova, F., Médard, J. J., Petitpré, C., Landy, M. A., Zhang, M. D., Harrer, P., Stendel, C., Stucka, R., Dusl, M., Kastriti, M. E., Croci, L., Lai, H. C., ... Chrast, R. (2019). PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis. Cell Reports, 26(13), 3484-3492.e4. https://doi.org/10.1016/j.celrep.2019.02.098

PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis. / Bartesaghi, Luca; Wang, Yiqiao; Fontanet, Paula; Wanderoy, Simone; Berger, Finja; Wu, Haohao; Akkuratova, Natalia; Bouçanova, Filipa; Médard, Jean Jacques; Petitpré, Charles; Landy, Mark A.; Zhang, Ming Dong; Harrer, Philip; Stendel, Claudia; Stucka, Rolf; Dusl, Marina; Kastriti, Maria Eleni; Croci, Laura; Lai, Helen C.; Consalez, Gian Giacomo; Pattyn, Alexandre; Ernfors, Patrik; Senderek, Jan; Adameyko, Igor; Lallemend, Francois; Hadjab, Saida; Chrast, Roman.

In: Cell Reports, Vol. 26, No. 13, 26.03.2019, p. 3484-3492.e4.

Research output: Contribution to journal › Article › peer-review

Bartesaghi, L, Wang, Y, Fontanet, P, Wanderoy, S, Berger, F, Wu, H, Akkuratova, N, Bouçanova, F, Médard, JJ, Petitpré, C, Landy, MA, Zhang, MD, Harrer, P, Stendel, C, Stucka, R, Dusl, M, Kastriti, ME, Croci, L, Lai, HC, Consalez, GG, Pattyn, A, Ernfors, P, Senderek, J, Adameyko, I, Lallemend, F, Hadjab, S & Chrast, R 2019, 'PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis', Cell Reports, vol. 26, no. 13, pp. 3484-3492.e4. https://doi.org/10.1016/j.celrep.2019.02.098

Bartesaghi, Luca ; Wang, Yiqiao ; Fontanet, Paula ; Wanderoy, Simone ; Berger, Finja ; Wu, Haohao ; Akkuratova, Natalia ; Bouçanova, Filipa ; Médard, Jean Jacques ; Petitpré, Charles ; Landy, Mark A. ; Zhang, Ming Dong ; Harrer, Philip ; Stendel, Claudia ; Stucka, Rolf ; Dusl, Marina ; Kastriti, Maria Eleni ; Croci, Laura ; Lai, Helen C. ; Consalez, Gian Giacomo ; Pattyn, Alexandre ; Ernfors, Patrik ; Senderek, Jan ; Adameyko, Igor ; Lallemend, Francois ; Hadjab, Saida ; Chrast, Roman. / PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis. In: Cell Reports. 2019 ; Vol. 26, No. 13. pp. 3484-3492.e4.

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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.). ",

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doi = "10.1016/j.celrep.2019.02.098",

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T1 - PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

AU - Bartesaghi, Luca

AU - Wang, Yiqiao

AU - Fontanet, Paula

AU - Wanderoy, Simone

AU - Berger, Finja

AU - Wu, Haohao

AU - Akkuratova, Natalia

AU - Bouçanova, Filipa

AU - Médard, Jean Jacques

AU - Petitpré, Charles

AU - Landy, Mark A.

AU - Zhang, Ming Dong

AU - Harrer, Philip

AU - Stendel, Claudia

AU - Stucka, Rolf

AU - Dusl, Marina

AU - Kastriti, Maria Eleni

AU - Croci, Laura

AU - Lai, Helen C.

AU - Consalez, Gian Giacomo

AU - Pattyn, Alexandre

AU - Ernfors, Patrik

AU - Senderek, Jan

AU - Adameyko, Igor

AU - Lallemend, Francois

AU - Hadjab, Saida

AU - Chrast, Roman

N1 - Funding Information: We thank Prof. Frances Lefcort for anti-chicken TRKA and TRKC antibodies, Prof. Tomas Hökfelt 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 Åke Wiberg Foundation , Karolinska Institutet (Faculty Funded Career Position), the Ragnar Söderberg Foundation (Ragnar Söderberg 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.).

PY - 2019/3/26

Y1 - 2019/3/26

N2 - 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.

AB - 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.

KW - Prdm12

KW - neural crest cells

KW - neurogenesis

KW - nociceptive neurons

KW - pain

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