@article{3355af00f1314f7eabc9ac2c6fc80523,
title = "Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans",
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.",
keywords = "LSN, Phox2a, anterolateral tract, autonomic, dI5, dorsal horn, lamina I, lamina V, pain, spinoparabrachial",
author = "Roome, {R. Brian} and Bourojeni, {Farin B.} and Bishakha Mona and Shima Rastegar-Pouyani and Raphael Blain and Annie Dumouchel and Charleen Salesse and Thompson, {W. Scott} and Megan Brookbank and Yorick Gitton and Lino Tessarollo and Martyn Goulding and Johnson, {Jane E.} and Marie Kmita and Alain Ch{\'e}dotal and Artur Kania",
note = "Funding Information: We thank Meirong Liang, Julie Cardin, Qinzhang Zhu, and Colleen Barrick for technical assistance; Laura Kus (GENSAT) for advice on transgenic mouse design; Caroline Grou and Virginie Calderon for bioinformatics analyses; J.-F. Brunet for the Phox2a and Phox2b antiserum and advice; Carmen Birchmeier for Lmx1b, Tlx3, and Lbx1 antisera; Jay Bikoff for the Pou6F2 antiserum; Laskaro Zagoraiou for Shox2 antiserum; Hanns Ulrich Zeilhofer for the Hoxb8Cre mice; Jeff Mogil, Yves de Koninck, and Stefano Stifani for discussions; and Jean-Fran?ois Brunet, Adam Hantman, Denis Jabaudon, Jeff Mogil, Michel Cayouette, Sonia Paixao, Samuel Ferland, and Feng Wang for comments on the manuscript. R.B.R. was a recipient of a PhD studentship from Fonds de Recherche du Qu?bec - Sant?. S.R.-P. received a studentship from McGill University's Healthy Brains, Healthy Lives (HBHL) initiative supported, in part, by the Canada First Research Excellence Fund. J.E.J. was supported by the National Institutes of Health grant R37 HD091856. A.C. was supported by the Agence Nationale de la Recherche and Inserm (transversal program HuDeCa). L.T. was supported by the Intramural Research Program of NCI, NIH. A.K. and M.K. were funded by operating and project grants from the Canadian Institutes of Health Research (PJT-162225, MOP-77556, PJT-153053, and PJT-159839 to A.K. and MOP-127110 and PJT-162143 to M.K.). Conceptualization, R.B.R. and A.K.; Methodology, R.B.R. B.M. R.B. C.S. J.E.J. A.D. and M.K.; Validation, R.B.R.; Formal Analysis, R.B.R. and B.M.; Investigation, R.B.R. F.B.B. B.M. S.R.-P. R.B. C.S. W.S.T. and M.B.; Resources, R.B.R. A.D. M.K. L.T. Y.G. M.G. and A.K.; Data Curation, R.B.R. B.M. and J.E.J.; Writing ? Original Draft, R.B.R.; Writing ? Review & Editing, R.B.R. F.B.B. S.R.-P. M.K. L.T. J.E.J. M.K. A.C. and A.K.; Visualization, R.B.R. B.M. and J.E.J.; Supervision, J.E.J. M.K. A.C. and A.K.; Project Administration, A.K.; Funding Acquisition, J.E.J. M.K. A.C. and A.K. The authors declare no competing interests. Funding Information: R.B.R. was a recipient of a PhD studentship from Fonds de Recherche du Qu{\'e}bec - Sant{\'e} . S.R.-P. received a studentship from McGill University {\textquoteright}s Healthy Brains, Healthy Lives (HBHL) initiative supported, in part, by the Canada First Research Excellence Fund . J.E.J. was supported by the National Institutes of Health grant R37 HD091856 . A.C. was supported by the Agence Nationale de la Recherche and Inserm (transversal program HuDeCa). L.T. was supported by the Intramural Research Program of NCI , NIH. A.K. and M.K. were funded by operating and project grants from the Canadian Institutes of Health Research ( PJT-162225 , MOP-77556 , PJT-153053 , and PJT-159839 to A.K. and MOP-127110 and PJT-162143 to M.K.). Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = nov,
day = "24",
doi = "10.1016/j.celrep.2020.108425",
language = "English (US)",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}