{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:58:40Z","timestamp":1790294320320,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,21]]},"group-title":"Neuroscience","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"MRC"},{"id":[{"id":"https:\/\/ror.org\/01khddn76","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Column of Hope"},{"name":"Wellcome Trust","id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Warwick","award":["Chancellor's Fellowship"],"award-info":[{"award-number":["Chancellor's Fellowship"]}],"id":[{"id":"https:\/\/ror.org\/01a77tt86","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,21]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The precise control of breathing is fundamental to vertebrate survival. Increased PCO\n                  <jats:sub>2<\/jats:sub>\n                  in blood and brain parenchyma causes an increase in both the frequency and volume of lung ventilation. We have previously demonstrated that CO\n                  <jats:sub>2<\/jats:sub>\n                  directly binds to connexin26 (Cx26) hemichannels causing them to open and allow release ATP. We now document the role of Cx26 as a direct physiological CO\n                  <jats:sub>2<\/jats:sub>\n                  sensor\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Here we describe a unique Cx26+ neural crest cell lineage that populates the ventral brainstem in the vicinity of the PreBoetz nucleus\/caudal CO2 chemosensory area during middle age and dies again in old age. Ablating Cx26 genetically specifically within this population of about 20 cells by two independent neural crest Cre-driver lines leads to a loss of local ATP release in the posterior chemosensory area as well as a 40% reduction in elevated tidal volume responses specifically in middle age, as measured by whole-body plethysmography. These\n                  <jats:italic>in vivo effects<\/jats:italic>\n                  change over a life-time: they directly mirror the arrival, wiring in middle age and later death of this cell population in old age. This is a first known example of a middle age change in cranial neural crest lineage composition and highlights the significant power of very few cells for global metabolism. Such lineage-dependent middle-age dynamics also impacts upon the evolution of eusociality: altricial naked pups of our common amniote\/synapsid ancestors were heated by by the breath of their (middle-aged) carers, sensing elevated CO\n                  <jats:sub>2<\/jats:sub>\n                  levels in hypercapnic burrows. Such mechanistic exaptation enabled small amniotes to sense and survive the lethal global CO\n                  <jats:sub>2<\/jats:sub>\n                  spikes during the Permo-Triassic and other extinction events.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.752084","type":"posted-content","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:55:15Z","timestamp":1790024115000},"source":"Crossref","is-referenced-by-count":0,"title":["A discrete Connexin26+ neural crest lineage emerges in mid-life and mediates enhanced central brainstem responses to elevated CO\n                  <sub>2<\/sub>\n                  levels for deep breathing"],"prefix":"10.64898","author":[{"given":"Xintao","family":"Zhang","sequence":"first","affiliation":[{"name":"University of Warwick, School of Life Sciences, Coventry CV4 7AL, UK"},{"name":"Warwick Neuroscience Group, University College London, London, UK"},{"name":"Laboratory of Systems Biomedicine and Evolution, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Warwick, School of Life Sciences, Coventry CV4 7AL, UK"},{"name":"Warwick Neuroscience Group, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M. 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