{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:59:47Z","timestamp":1788926387082,"version":"build-2803163510"},"reference-count":41,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"crossref","award":["P2022\/BMD-7393"],"award-info":[{"award-number":["P2022\/BMD-7393"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["RTI2018-098520-B-I00"],"award-info":[{"award-number":["RTI2018-098520-B-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["PID2020-115274RB-I00"],"award-info":[{"award-number":["PID2020-115274RB-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["PID2021-122600OB-I00"],"award-info":[{"award-number":["PID2021-122600OB-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Developmental senescence is a form of programmed senescence that contributes to morphogenesis during embryonic development. We showed recently that the SIX1 homeoprotein, an essential regulator of organogenesis, is also a repressor of adult cellular senescence. Alterations in the SIX\/EYA pathway are linked to the human branchio-oto-renal (BOR) syndrome, a rare congenital disorder associated with defects in the ears, kidneys and branchial arches. Here, we have used Six1-deficient mice, an animal model of the BOR syndrome, to investigate whether dysfunction of senescence underpins the developmental defects associated with SIX1 deficiency. We have focused on the developing inner ear, an organ with physiological developmental senescence that is severely affected in Six1-deficient mice and BOR patients. We show aberrant levels and distribution of senescence markers in Six1-deficient inner ears concomitant with defective morphogenesis of senescent structures. Transcriptomic analysis and ex vivo assays support a link between aberrant senescence and altered morphogenesis in this model, associated with deregulation of the TGF\u03b2\/BMP pathway. Our results show that misregulation of embryo senescence may lead to genetic developmental disorders, significantly expanding the connection between senescence and disease.<\/jats:p>","DOI":"10.1242\/dev.200903","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T07:21:29Z","timestamp":1680679289000},"source":"Crossref","is-referenced-by-count":11,"title":["Dysfunction of programmed embryo senescence is linked to genetic developmental defects"],"prefix":"10.1242","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6102-3754","authenticated-orcid":false,"given":"Cristina","family":"de Lope","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-532X","authenticated-orcid":false,"given":"Rebeca","family":"Garc\u00eda-Lucena","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Magari\u00f1os","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Madrid 2 Biology Department , , 28049 Madrid , Spain"},{"name":"Rare Diseases Networking Biomedical Research Centre (CIBERER), CIBER, Carlos III Institute of Health 3 , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-8373","authenticated-orcid":false,"given":"Yolanda","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Madrid 2 Biology Department , , 28049 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-0381","authenticated-orcid":false,"given":"Nuria","family":"Casa-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-6758","authenticated-orcid":false,"given":"Nuria","family":"Contreras","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9924-6913","authenticated-orcid":false,"given":"Carmen","family":"Escudero-Iriarte","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-0500","authenticated-orcid":false,"given":"Isabel","family":"Varela-Nieto","sequence":"additional","affiliation":[{"name":"Rare Diseases Networking Biomedical Research Centre (CIBERER), CIBER, Carlos III Institute of Health 3 , 28029 Madrid , Spain"},{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 4 Neuropathology of Hearing and Myelinopathies Lab , , 28029 Madrid , Spain"},{"name":"Hospital La Paz Institute for Health Research (IdiPAZ) 5 , 28046 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7795-0029","authenticated-orcid":false,"given":"Pascal","family":"Maire","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, Institut Cochin, INSERM, CNRS 6 , 75014 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-7679","authenticated-orcid":false,"given":"Ignacio","family":"Palmero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d CSIC-UAM 1 Cell Senescence and Tumor Suppression Lab , , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"2023050312513735700_DEV200903C1","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ncb2784","article-title":"A complex secretory program orchestrated by the inflammasome controls paracrine senescence","volume":"15","author":"Acosta","year":"2013","journal-title":"Nat. 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