PT - JOURNAL ARTICLE AU - R. Brian Roome AU - Farin B. Bourojeni AU - Bishakha Mona AU - Shima Rastegar-Pouyani AU - Raphael Blain AU - Annie Dumouchel AU - Charleen Salesse AU - W. Scott Thompson AU - Megan Brookbank AU - Yorick Gitton AU - Lino Tessarollo AU - Martyn Goulding AU - Jane E. Johnson AU - Marie Kmita AU - Alain Chédotal AU - Artur Kania TI - Phox2a defines a developmental origin of the anterolateral system in mice and humans AID - 10.1101/2020.06.10.144659 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.10.144659 4099 - http://biorxiv.org/content/early/2020/06/11/2020.06.10.144659.short 4100 - http://biorxiv.org/content/early/2020/06/11/2020.06.10.144659.full 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 virtually all 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 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 foetal spinal cord. The developmental expression of Phox2a as a uniting feature of anterolateral system neurons suggests a link between nociception and autonomic nervous system function.Competing Interest StatementThe authors have declared no competing interest.