{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:40:05Z","timestamp":1791225605320,"version":"4.1.0"},"reference-count":45,"publisher":"The Company of Biologists","issue":"17","license":[{"start":{"date-parts":[[1999,9,1]],"date-time":"1999-09-01T00:00:00Z","timestamp":936144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Integrins \u03b16\u03b21 and \u03b16\u03b24 are cell surface receptors for laminins. Integrin \u03b16-null mice die at birth with severe skin blistering and defects in the cerebral cortex and in the retina. Integrin \u03b13\u03b21 can associate with laminins and other ligands. Integrin \u03b13-null mice also die at birth, with kidney and lung defects at late stages of development, and moderate skin blistering. To investigate possible overlapping functions between \u03b13 and \u03b16 integrins, we analyzed the phenotype of compound \u03b13\u2212\/\u2212\/\u03b16\u2212\/\u2212 mutant embryos. Double homozygous mutant embryos were growth-retarded and displayed several developmental defects not observed in the single mutant animals. First, limb abnormalities characterized by an absence of digit separation and the fusion of preskeletal elements were observed. Further analyses indicated a defect in the apical ectodermal ridge, an essential limb organizing center. In the double mutant, the ridge appeared flattened, and ridge cells did not show a columnar morphology. A strong reduction in ridge cell proliferation and alterations of the basal lamina underlying the ectoderm were observed. These results suggest that \u03b13 and \u03b16 integrins are required for the organization or compaction of presumptive apical ectodermal ridge cells into a distinct differentiated structure. Additional defects were present: an absence of neural tube closure, bilateral lung hypoplasia, and several abnormalities in the urogenital tract. Finally, an aggravation of brain and eye lamination defects was observed. The presence of novel phenotypes in double mutant embryos demonstrates the synergism between \u03b13 and \u03b16 integrins and their essential roles in multiple processes during embryogenesis.<\/jats:p>","DOI":"10.1242\/dev.126.17.3957","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:48:41Z","timestamp":1619408921000},"page":"3957-3968","source":"Crossref","is-referenced-by-count":188,"title":["Synergistic activities of \u03b13 and \u03b16 integrins are required during apical ectodermal ridge formation and organogenesis in the mouse"],"prefix":"10.1242","volume":"126","author":[{"given":"Ad\u00e8le","family":"De Arcangelis","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire 1 , CNRS\/INSERM\/ULP, BP 163, 67404 Illkirch, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mark","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire 1 , CNRS\/INSERM\/ULP, BP 163, 67404 Illkirch, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Kreidberg","sequence":"additional","affiliation":[{"name":"Department of Medicine 2 , Children\u2019s Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Sorokin","sequence":"additional","affiliation":[{"name":"IZKF 3 , Nikolaus Fiebiger Center, Friedrich Alexander Universit\u00e4t, Erlangen-Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Georges-Labouesse","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire 1 , CNRS\/INSERM\/ULP, BP 163, 67404 Illkirch, CU de Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,9,1]]},"reference":[{"key":"2024071014361261800_DEVELOP_126_17_3957C1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0896-6273(00)81089-2","article-title":"Distinct functions of alpha3 and alpha(v) integrin receptors in neuronal migration and laminar organization of the cerebral cortex","volume":"22","author":"Anton","year":"1999","journal-title":"Neuron"},{"key":"2024071014361261800_DEVELOP_126_17_3957C2","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1006\/dbio.1996.0317","article-title":"The extracellular matrix in epithelial biology: shared molecules and common themes in distant phyla","volume":"180","author":"Ashkenas","year":"1996","journal-title":"Dev.Biol"},{"key":"2024071014361261800_DEVELOP_126_17_3957C3","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0092-8674(91)90092-D","article-title":"tEpiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes","volume":"65","author":"Carter","year":"1991","journal-title":"Cell"},{"key":"2024071014361261800_DEVELOP_126_17_3957C4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1006\/dbio.1998.8938","article-title":"Defect in the maintenance of the apical ectodermal ridge in the Dactylaplasia mouse","volume":"201","author":"Crackower","year":"1998","journal-title":"Dev. 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