{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:44:31Z","timestamp":1792727071235,"version":"4.5.0"},"reference-count":91,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,11,19]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Human mutations in SOX9 lead to several congenital disorders, including campomelic dysplasia. Babies born with this condition often die of respiratory distress; however, defects in lung development have thus far not been reported in mouse models. Here, we report that epithelial-specific deletion of Sox9 leads to developmental abnormalities in the lung during branching morphogenesis. We demonstrate that Sox9 plays multiple roles in the lung epithelium, balancing proliferation and differentiation and regulating the extracellular matrix. Therefore, our work highlights a role for Sox9 during lung branching morphogenesis, making this a useful model to study defects associated with a congenital disorder affecting humans.<\/jats:p>","DOI":"10.1073\/pnas.1311847110","type":"journal-article","created":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T20:58:48Z","timestamp":1383598728000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":272,"title":["Sox9 plays multiple roles in the lung epithelium during branching morphogenesis"],"prefix":"10.1073","volume":"110","author":[{"given":"Briana E.","family":"Rockich","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Hrycaj","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung Ping","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda S.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A. H.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janel L.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deneen M.","family":"Wellik","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology and"},{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200;"},{"name":"Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109-2200"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Spence","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology and"},{"name":"Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-2200;"},{"name":"Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109-2200"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,11,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22504"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.12.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22482"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000159570.01327.ED"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.11.012"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.11.030"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.02.019"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/org.7.3.18462"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq104"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.061762"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152238499"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.037317"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01678"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","unstructured":"Perl AK Kist R Shan Z Scherer G Whitsett JA. (2005) Normal lung development and function afterSox9 inactivation in the respiratory epithelium. Genesis 41(1):23\u201332.","DOI":"10.1002\/gene.20093"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.23823"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610770104"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.12.001"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.046177"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2011.92"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.6.415"},{"key":"e_1_3_3_22_2","first-page":"1028","article-title":"Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal","volume":"57","author":"Kwok C","year":"1995","unstructured":"C Kwok, et al., Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal. Am J Hum Genet 57, 1028\u20131036 (1995).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg158"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1950040313"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320150103"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.07.034"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609217104"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704054104"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.020"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10165-008-0048-x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.05.019"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.2741\/2359"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704152"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200311021"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10050"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.024"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510839103"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.23961"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00117-9"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.12.2695"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68782"},{"key":"e_1_3_3_42_2","first-page":"L100","article-title":"Processing of hydrophobic pulmonary surfactant protein B in rat type II cells","volume":"257","author":"Weaver TE","year":"1989","unstructured":"TE Weaver, JA Whitsett, Processing of hydrophobic pulmonary surfactant protein B in rat type II cells. Am J Physiol 257, L100\u2013L108 (1989).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.12.4007"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.130.6.732"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02033"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20237"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2002.6418"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.423905"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092053"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001176"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23324"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.08.020"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.04.038"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.065110"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.015495"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.06.005"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044871"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22032"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.02.031"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.02.002"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.101907"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029982"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2005.00902.x"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707390200"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1159\/000106775"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060899"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq426"},{"key":"e_1_3_3_68_2","doi-asserted-by":"crossref","unstructured":"AH Schulick et al. (1998) Overexpression of transforming growth factor \u03b21 in arterial endothelium causes hyperplasia apoptosis and cartilaginous metaplasia. Proc Natl Acad Sci U S A 95(12):6983\u20136988.","DOI":"10.1073\/pnas.95.12.6983"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010113"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001650102"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.692"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200910095"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.05.012"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2010.010086"},{"key":"e_1_3_3_75_2","first-page":"4439","article-title":"PTEN loss induces epithelial\u2014mesenchymal transition in human colon cancer cells","volume":"29","author":"Bowen KA","year":"2009","unstructured":"KA Bowen, et al., PTEN loss induces epithelial\u2014mesenchymal transition in human colon cancer cells. Anticancer Res 29, 4439\u20134449 (2009).","journal-title":"Anticancer Res"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5915"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e3181b7fc8d"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.078733"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.722"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056499"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.8.1253"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni051"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-019-5_5"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09691"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.05.012"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2005.12.002"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1139"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.2.531"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22134"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e328355f260"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1311847110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:32:48Z","timestamp":1649806368000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1311847110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,4]]},"references-count":91,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2013,11,19]]}},"alternative-id":["10.1073\/pnas.1311847110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1311847110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,4]]},"assertion":[{"value":"2013-11-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}