{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:08:17Z","timestamp":1790798897494,"version":"4.1.0"},"reference-count":66,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DEQ20170336764"],"award-info":[{"award-number":["DEQ20170336764"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010299","name":"Institut pour la Recherche sur la Moelle \u00e9pini\u00e8re et l'Enc\u00e9phale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010299","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,10,20]]},"abstract":"<jats:p>\n                    Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT,\n                    <jats:italic>\n                      Spi1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    (Pu.1 WT)) mouse (\n                    <jats:italic>Mus musculus<\/jats:italic>\n                    ) brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preB\u00f6tzinger complex (preB\u00f6tC)). In transgenic mice depleted of microglia (\n                    <jats:italic>\n                      Spi1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    (Pu.1 KO) mutant), we performed anatomical staining, calcium imaging, and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preB\u00f6tC at E16.5, and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preB\u00f6tC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5\n                    <jats:italic>\n                      Spi1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.\n                  <\/jats:p>","DOI":"10.7554\/elife.80352","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T02:15:10Z","timestamp":1666318510000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80352","source":"Crossref","is-referenced-by-count":9,"title":["Microglia shape the embryonic development of mammalian respiratory networks"],"prefix":"10.7554","volume":"11","author":[{"given":"Marie-Jeanne","family":"Cabirol","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01a6zh966","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Neurosciences Cognitives et Int\u00e9gratives d\u2019Aquitaine, CNRS, Universit\u00e9 de Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cardoit","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01a6zh966","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Neurosciences Cognitives et Int\u00e9gratives d\u2019Aquitaine, CNRS, Universit\u00e9 de Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Courtand","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01a6zh966","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Neurosciences Cognitives et Int\u00e9gratives d\u2019Aquitaine, CNRS, Universit\u00e9 de Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Eve","family":"Mayeur","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}],"name":"MeLis INSERM U1314-CNRS UMR 5284, Facult\u00e9 Rockefeller","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7487-4638","authenticated-orcid":true,"given":"John","family":"Simmers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01a6zh966","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Neurosciences Cognitives et Int\u00e9gratives d\u2019Aquitaine, CNRS, Universit\u00e9 de Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Pascual","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}],"name":"MeLis INSERM U1314-CNRS UMR 5284, Facult\u00e9 Rockefeller","place":["Lyon, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-1724","authenticated-orcid":true,"given":"Muriel","family":"Thoby-Brisson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01a6zh966","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut de Neurosciences Cognitives et Int\u00e9gratives d\u2019Aquitaine, CNRS, Universit\u00e9 de Bordeaux","place":["Bordeaux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/nature18944","article-title":"A novel excitatory network for the control of breathing","volume":"536","author":"Anderson","year":"2016","journal-title":"Nature"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.1002\/glia.23499","article-title":"Embryonic macrophages and microglia ablation alter the development of dorsal root ganglion sensory neurons in mouse embryos","volume":"66","author":"Angelim","year":"2018","journal-title":"Glia"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0165-3806(91)90231-7","article-title":"The distribution of microglia and cell death in the fetal rat forebrain","volume":"58","author":"Ashwell","year":"1991","journal-title":"Brain Research. 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