{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:31:20Z","timestamp":1790339480159,"version":"4.1.0"},"reference-count":50,"publisher":"The Royal Society","issue":"1529","license":[{"start":{"date-parts":[[2009,9,12]],"date-time":"2009-09-12T00:00:00Z","timestamp":1252713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2009,9,12]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Hox<\/jats:italic>\n                    genetic network plays a key role in the anteroposterior patterning of the rhombencephalon at pre- and early-segmental stages of development of the neural tube. In the mouse, it controls development of the entire brainstem respiratory neuronal network, including the pons, the parafacial respiratory group (pFRG) and the pre-B\u00f6tzinger complex (preB\u00f6tC). Inactivation of\n                    <jats:italic>Krox20\/Egr2<\/jats:italic>\n                    eliminates the pFRG activity, thereby causing life-threatening neonatal apnoeas alternating with respiration at low frequency. Another respiratory abnormality, the complete absence of breathing, is induced when neuronal synchronization fails to develop in the preB\u00f6tC. The present paper summarizes data on a third type of respiratory deficits induced by altering\n                    <jats:italic>Hox<\/jats:italic>\n                    function at pontine levels. Inactivation of\n                    <jats:italic>Hoxa2<\/jats:italic>\n                    , the most rostrally expressed Hox gene in the hindbrain, disturbs embryonic development of the pons and alters neonatal inspiratory shaping without affecting respiratory frequency and apnoeas. The same result is obtained by the\n                    <jats:italic>Phox2a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mutation modifying the number of petrosal chemoafferent neurons, by eliminating acetylcholinesterase and by altering\n                    <jats:italic>Hox<\/jats:italic>\n                    -dependent development of the pons with retinoic acid administration at embryonic day 7.5. In addition, embryos treated with retinoic acid provide a mouse model for hyperpnoeic episodic breathing, widely reported in pre-term neonates, young girls with Rett's syndrome, patients with Joubert syndrome and adults with Cheyne\u2013Stokes respiration. We conclude that specific respiratory deficits\n                    <jats:italic>in vivo<\/jats:italic>\n                    are assignable to anteroposterior segments of the brainstem, suggesting that the adult respiratory neuronal network is functionally organized according to the rhombomeric,\n                    <jats:italic>Hox<\/jats:italic>\n                    -dependent segmentation of the brainstem in embryos.\n                  <\/jats:p>","DOI":"10.1098\/rstb.2009.0090","type":"journal-article","created":{"date-parts":[[2009,8,3]],"date-time":"2009-08-03T06:03:28Z","timestamp":1249279408000},"page":"2469-2476","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Developmental basis of the rostro-caudal organization of the brainstem respiratory rhythm generator"],"prefix":"10.1098","volume":"364","author":[{"given":"J.","family":"Champagnat","sequence":"first","affiliation":[{"name":"Centre de Recherche de Gif, UPR 2216 (Neurobiologie G\u00e9n\u00e9tique et Int\u00e9grative), IFR 2118 (Institut de Neurobiologie Alfred Fessard), CNRS, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. P.","family":"Morin-Surun","sequence":"additional","affiliation":[{"name":"Centre de Recherche de Gif, UPR 2216 (Neurobiologie G\u00e9n\u00e9tique et Int\u00e9grative), IFR 2118 (Institut de Neurobiologie Alfred Fessard), CNRS, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Fortin","sequence":"additional","affiliation":[{"name":"Centre de Recherche de Gif, UPR 2216 (Neurobiologie G\u00e9n\u00e9tique et Int\u00e9grative), IFR 2118 (Institut de Neurobiologie Alfred Fessard), CNRS, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Thoby-Brisson","sequence":"additional","affiliation":[{"name":"Centre de Recherche de Gif, UPR 2216 (Neurobiologie G\u00e9n\u00e9tique et Int\u00e9grative), IFR 2118 (Institut de Neurobiologie Alfred Fessard), CNRS, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2009,9,12]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1995.75.1.1"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10145"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2003.11.002"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2005.02.014"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20271"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2003.10.006"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.03.002"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2004.10.014"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.12.001"},{"key":"e_1_3_2_11_1","first-page":"175","volume-title":"Respiratory pharmacology","author":"Brimblecombe R. 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