Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans

R. Brian Roome; Farin B. Bourojeni; Bishakha Mona; Shima Rastegar-Pouyani; Raphael Blain; Annie Dumouchel; Charleen Salesse; W. Scott Thompson; Megan Brookbank; Yorick Gitton; Lino Tessarollo; Martyn Goulding; Jane E. Johnson; Marie Kmita; Alain Chédotal; Artur Kania

doi:10.1016/j.celrep.2020.108425

Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans

R. Brian Roome, Farin B. Bourojeni, Bishakha Mona, Shima Rastegar-Pouyani, Raphael Blain, Annie Dumouchel, Charleen Salesse, W. Scott Thompson, Megan Brookbank, Yorick Gitton, Lino Tessarollo, Martyn Goulding, Jane E. Johnson, Marie Kmita, Alain Chédotal, Artur Kania

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

23 Scopus citations

Abstract

Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.

Original language	English (US)
Article number	108425
Journal	Cell Reports
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2020.108425
State	Published - Nov 24 2020

Keywords

LSN
Phox2a
anterolateral tract
autonomic
dI5
dorsal horn
lamina I
lamina V
pain
spinoparabrachial

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2020.108425

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Roome, R. B., Bourojeni, F. B., Mona, B., Rastegar-Pouyani, S., Blain, R., Dumouchel, A., Salesse, C., Thompson, W. S., Brookbank, M., Gitton, Y., Tessarollo, L., Goulding, M., Johnson, J. E., Kmita, M., Chédotal, A., & Kania, A. (2020). Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans. Cell Reports, 33(8), Article 108425. https://doi.org/10.1016/j.celrep.2020.108425

Roome, RB, Bourojeni, FB, Mona, B, Rastegar-Pouyani, S, Blain, R, Dumouchel, A, Salesse, C, Thompson, WS, Brookbank, M, Gitton, Y, Tessarollo, L, Goulding, M, Johnson, JE, Kmita, M, Chédotal, A & Kania, A 2020, 'Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans', Cell Reports, vol. 33, no. 8, 108425. https://doi.org/10.1016/j.celrep.2020.108425

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abstract = "Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.",

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AU - Blain, Raphael

AU - Dumouchel, Annie

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AU - Thompson, W. Scott

AU - Brookbank, Megan

AU - Gitton, Yorick

AU - Tessarollo, Lino

AU - Goulding, Martyn

AU - Johnson, Jane E.

AU - Kmita, Marie

AU - Chédotal, Alain

AU - Kania, Artur

PY - 2020/11/24

Y1 - 2020/11/24

N2 - Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.

AB - Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.

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Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans

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