{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:49:19Z","timestamp":1776919759750,"version":"3.51.2"},"reference-count":76,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["P01HD093363"],"award-info":[{"award-number":["P01HD093363"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL141174"],"award-info":[{"award-number":["R01HL141174"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["F30HL142201"],"award-info":[{"award-number":["F30HL142201"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["T32HL0077521"],"award-info":[{"award-number":["T32HL0077521"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL144774"],"award-info":[{"award-number":["R01HL144774"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL141174"],"award-info":[{"award-number":["R01HL141174"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL149631"],"award-info":[{"award-number":["R01HL149631"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["T32 GM063483"],"award-info":[{"award-number":["T32 GM063483"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["P30DK0778392"],"award-info":[{"award-number":["P30DK0778392"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple HH\/Gli mouse mutants, including one that mimics Pallister\u2013Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage-tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH\/Gli signaling results in (1) loss of Foxf1, which in turn is required to support Sox9+ chondrocyte progenitors, and (2) a dramatic reduction in Rspo2, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal an HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.046573","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T17:17:28Z","timestamp":1608139048000},"source":"Crossref","is-referenced-by-count":21,"title":["Disruption of a Hedgehog-Foxf1-Rspo2 signaling axis leads to tracheomalacia and a loss of Sox9+ tracheal chondrocytes"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-5402","authenticated-orcid":false,"given":"Talia","family":"Nasr","sequence":"first","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea M.","family":"Holderbaum","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-6570","authenticated-orcid":false,"given":"Praneet","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunal","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Kinney","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keziah","family":"Daniels","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0937-4474","authenticated-orcid":false,"given":"Stephen L.","family":"Trisno","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Ustiyan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229"},{"name":"Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-848X","authenticated-orcid":false,"given":"James M.","family":"Wells","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-5223","authenticated-orcid":false,"given":"Debora","family":"Sinner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir V.","family":"Kalinichenko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229"},{"name":"Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3217-3590","authenticated-orcid":false,"given":"Aaron M.","family":"Zorn","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"2021042623034897600_DMM046573C1","doi-asserted-by":"publisher","first-page":"dev185256","DOI":"10.1242\/dev.185256","article-title":"Cardiopharyngeal mesoderm origins of musculoskeletal and connective tissues in the mammalian pharynx","volume":"147","author":"Adachi","year":"2020","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C2","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1101\/gad.1951710","article-title":"Interactions between Hedgehog proteins and their binding partners come into view","volume":"24","author":"Beachy","year":"2010","journal-title":"Genes Dev."},{"key":"2021042623034897600_DMM046573C3","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1242\/dev.013359","article-title":"R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis","volume":"135","author":"Bell","year":"2008","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C4","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1093\/hmg\/ddm061","article-title":"SOX9cre1, a cis-acting regulatory element located 1.1 Mb upstream of SOX9, mediates its enhancement through the SHH pathway","volume":"16","author":"Bien-Willner","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"2021042623034897600_DMM046573C5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1083\/jcb.200311021","article-title":"SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes","volume":"166","author":"Blache","year":"2004","journal-title":"J. Cell Biol."},{"key":"2021042623034897600_DMM046573C6","doi-asserted-by":"publisher","first-page":"e1006951","DOI":"10.1371\/journal.pgen.1006951","article-title":"A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development","volume":"13","author":"Bohnenpoll","year":"2017","journal-title":"PLoS Genet."},{"key":"2021042623034897600_DMM046573C7","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1378\/chest.128.5.3391","article-title":"Tracheomalacia and bronchomalacia in children: incidence and patient characteristics","volume":"128","author":"Boogaard","year":"2005","journal-title":"Chest"},{"key":"2021042623034897600_DMM046573C8","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1093\/hmg\/11.9.1129","article-title":"Pallister-Hall syndrome phenotype in mice mutant for Gli3","volume":"11","author":"Bose","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2021042623034897600_DMM046573C9","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1242\/dev.110254","article-title":"Crucial requirement of ERK\/MAPK signaling in respiratory tract development","volume":"141","author":"Boucherat","year":"2015","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C10","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/nrm3598","article-title":"The mechanisms of Hedgehog signalling and its roles in development and disease","volume":"14","author":"Briscoe","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042623034897600_DMM046573C11","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.ydbio.2015.08.017","article-title":"Wnt4 is essential to normal mammalian lung development","volume":"406","author":"Caprioli","year":"2015","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C12","doi-asserted-by":"publisher","first-page":"11452","DOI":"10.1073\/pnas.1106083108","article-title":"R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt\/\u03b2-catenin signaling","volume":"108","author":"Carmon","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042623034897600_DMM046573C13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/nature10337","article-title":"Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling","volume":"476","author":"de Lau","year":"2011","journal-title":"Nature"},{"key":"2021042623034897600_DMM046573C14","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1242\/bio.019208","article-title":"Lethal lung hypoplasia and vascular defects in mice with conditional Foxf1 overexpression","volume":"5","author":"Dharmadhikari","year":"2016","journal-title":"Biol. Open"},{"key":"2021042623034897600_DMM046573C15","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1242\/dev.053694","article-title":"Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2","volume":"138","author":"Domyan","year":"2011","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C16","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.semcdb.2014.05.010","article-title":"Transcriptional regulation of graded Hedgehog signaling","volume":"33","author":"Falkenstein","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"2021042623034897600_DMM046573C17","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.sempedsurg.2016.02.008","article-title":"Pediatric tracheomalacia","volume":"25","author":"Fraga","year":"2016","journal-title":"Semin. Pediatr. Surg."},{"key":"2021042623034897600_DMM046573C18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ydbio.2018.02.002","article-title":"Notum attenuates Wnt\/\u03b2-catenin signaling to promote tracheal cartilage patterning","volume":"436","author":"Gerhardt","year":"2018","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C19","doi-asserted-by":"publisher","first-page":"e37137","DOI":"10.1371\/journal.pone.0037137","article-title":"LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor","volume":"7","author":"Gong","year":"2012","journal-title":"PloS one"},{"key":"2021042623034897600_DMM046573C20","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.devcel.2009.06.005","article-title":"Wnt2\/2b and \u03b2-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut","volume":"17","author":"Goss","year":"2009","journal-title":"Dev. Cell"},{"key":"2021042623034897600_DMM046573C21","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1006\/dbio.2000.9732","article-title":"Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures","volume":"222","author":"H\u00e9bert","year":"2000","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C22","doi-asserted-by":"publisher","first-page":"19444","DOI":"10.1073\/pnas.1313223110","article-title":"Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways","volume":"110","author":"Hines","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042623034897600_DMM046573C23","doi-asserted-by":"publisher","first-page":"e1004604","DOI":"10.1371\/journal.pgen.1004604","article-title":"Foxf genes integrate tbx5 and hedgehog pathways in the second heart field for cardiac septation","volume":"10","author":"Hoffmann","year":"2014","journal-title":"PLoS Genet."},{"key":"2021042623034897600_DMM046573C24","doi-asserted-by":"publisher","first-page":"28477","DOI":"10.1074\/jbc.M113.478974","article-title":"The transcription factor Foxf1 binds to serum response factor and myocardin to regulate gene transcription in visceral smooth muscle cells","volume":"288","author":"Hoggatt","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021042623034897600_DMM046573C25","doi-asserted-by":"publisher","first-page":"dev171496","DOI":"10.1242\/dev.171496","article-title":"Wnt\/Fgf crosstalk is required for the specification of basal cells in the mouse trachea","volume":"146","author":"Hou","year":"2019","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C26","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1053\/jpsu.2003.50005","article-title":"Role of Sonic hedgehog in the development of the trachea and oesophagus","volume":"38","author":"Ioannides","year":"2003","journal-title":"J. Pediatr. Surg."},{"key":"2021042623034897600_DMM046573C27","doi-asserted-by":"publisher","first-page":"5703","DOI":"10.1096\/fj.201701581R","article-title":"Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice","volume":"32","author":"Jia","year":"2018","journal-title":"FASEB J."},{"key":"2021042623034897600_DMM046573C28","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1086\/429346","article-title":"Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations","volume":"76","author":"Johnston","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"2021042623034897600_DMM046573C29","doi-asserted-by":"publisher","first-page":"512","DOI":"10.3389\/fped.2019.00512","article-title":"Tracheomalacia and Tracheobronchomalacia in pediatrics: an overview of evaluation, medical management, and surgical treatment","volume":"7","author":"Kamran","year":"2019","journal-title":"Front. Pediatr."},{"key":"2021042623034897600_DMM046573C30","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.devcel.2004.07.019","article-title":"R-Spondin2 is a secreted activator of Wnt\/\u03b2-catenin signaling and is required for Xenopus myogenesis","volume":"7","author":"Kazanskaya","year":"2004","journal-title":"Dev. Cell"},{"key":"2021042623034897600_DMM046573C31","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1091\/mbc.e08-02-0187","article-title":"R-Spondin family members regulate the Wnt pathway by a common mechanism","volume":"19","author":"Kim","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"2021042623034897600_DMM046573C32","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1038\/s41467-018-05189-2","article-title":"Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus","volume":"9","author":"Kishimoto","year":"2018","journal-title":"Nat. Commun."},{"key":"2021042623034897600_DMM046573C76","doi-asserted-by":"publisher","author":"Kist","year":"2002","DOI":"10.1002\/gene.10050"},{"key":"2021042623034897600_DMM046573C33","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1242\/dev.105536","article-title":"A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation","volume":"142","author":"Kozhemyakina","year":"2015","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C34","doi-asserted-by":"publisher","first-page":"e55526","DOI":"10.7554\/eLife.55526","article-title":"Delineating the early transcriptional specification of the mammalian trachea and esophagus","volume":"9","author":"Kuwahara","year":"2020","journal-title":"eLife"},{"key":"2021042623034897600_DMM046573C35","doi-asserted-by":"publisher","first-page":"e33126","DOI":"10.7554\/eLife.33126","article-title":"R-spondins can potentiate WNT signaling without LGRs","volume":"7","author":"Lebensohn","year":"2018","journal-title":"eLife"},{"key":"2021042623034897600_DMM046573C36","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ceb.2019.07.008","article-title":"SOX9 in cartilage development and disease","volume":"61","author":"Lefebvre","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021042623034897600_DMM046573C37","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ydbio.2013.04.026","article-title":"The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling","volume":"379","author":"Lewis","year":"2013","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C38","doi-asserted-by":"publisher","first-page":"e50670","DOI":"10.7554\/eLife.50670","article-title":"GLI transcriptional repression regulates tissue-specific enhancer activity in response to Hedgehog signaling","volume":"9","author":"Lex","year":"2020","journal-title":"eLife"},{"key":"2021042623034897600_DMM046573C39","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1006\/dbio.2002.0729","article-title":"Wnt5a participates in distal lung morphogenesis","volume":"248","author":"Li","year":"2002","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C40","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.ydbio.2004.03.009","article-title":"Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis","volume":"270","author":"Li","year":"2004","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ydbio.2008.07.021","article-title":"Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis","volume":"322","author":"Li","year":"2008","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C42","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/1717","article-title":"Sonic hedgehog is essential to foregut development","volume":"20","author":"Litingtung","year":"1998","journal-title":"Nat. Genet."},{"key":"2021042623034897600_DMM046573C43","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nature01033","article-title":"Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity","volume":"418","author":"Litingtung","year":"2002","journal-title":"Nature"},{"key":"2021042623034897600_DMM046573C44","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s11010-014-1963-0","article-title":"Overexpression of Wnt11 promotes chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in synergism with TGF-\u03b2","volume":"390","author":"Liu","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"2021042623034897600_DMM046573C45","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1242\/dev.128.24.5099","article-title":"Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation","volume":"128","author":"Long","year":"2001","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C46","doi-asserted-by":"publisher","first-page":"5936","DOI":"10.1074\/jbc.M808103200","article-title":"FoxF1 and FoxL1 link hedgehog signaling and the control of epithelial proliferation in the developing stomach and intestine","volume":"284","author":"Madison","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021042623034897600_DMM046573C47","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1242\/dev.128.12.2397","article-title":"Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations","volume":"128","author":"Mahlapuu","year":"2001","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C48","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/dvdy.20105","article-title":"Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung","volume":"231","author":"Miller","year":"2004","journal-title":"Dev. Dyn."},{"key":"2021042623034897600_DMM046573C49","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1006\/dbio.1999.9234","article-title":"Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(\u2212\/\u2212) mouse embryos","volume":"209","author":"Minoo","year":"1999","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C50","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/1711","article-title":"Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus","volume":"20","author":"Motoyama","year":"1998","journal-title":"Nat. Genet."},{"key":"2021042623034897600_DMM046573C51","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A global double-fluorescent Cre reporter mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genesis"},{"key":"2021042623034897600_DMM046573C52","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.devcel.2019.11.003","article-title":"Endosome-mediated epithelial remodeling downstream of Hedgehog-Gli is required for tracheoesophageal separation","volume":"51","author":"Nasr","year":"2019","journal-title":"Dev. Cell"},{"key":"2021042623034897600_DMM046573C53","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1002\/dvdy.22192","article-title":"Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage","volume":"239","author":"Park","year":"2010","journal-title":"Dev. Dyn."},{"key":"2021042623034897600_DMM046573C54","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1242\/dev.003855","article-title":"Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm","volume":"134","author":"Que","year":"2007","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C55","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1242\/dev.034629","article-title":"Multiple roles for Sox2 in the developing and adult mouse trachea","volume":"136","author":"Que","year":"2009","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C56","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1242\/dev.015495","article-title":"Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme","volume":"135","author":"Rajagopal","year":"2008","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C57","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ram\u00edrez","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021042623034897600_DMM046573C58","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.celrep.2016.05.060","article-title":"A retinoic acid-Hedgehog cascade coordinates mesoderm-inducing signals and endoderm competence during lung specification","volume":"16","author":"Rankin","year":"2016","journal-title":"Cell Rep."},{"key":"2021042623034897600_DMM046573C59","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1161\/CIRCRESAHA.115.304382","article-title":"FOXF1 transcription factor is required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells","volume":"115","author":"Ren","year":"2014","journal-title":"Circ. Res."},{"key":"2021042623034897600_DMM046573C60","doi-asserted-by":"publisher","first-page":"e40976","DOI":"10.1371\/journal.pone.0040976","article-title":"R-Spondin potentiates Wnt\/\u03b2-catenin signaling through orphan receptors LGR4 and LGR5","volume":"7","author":"Ruffner","year":"2012","journal-title":"PLoS ONE"},{"key":"2021042623034897600_DMM046573C61","doi-asserted-by":"publisher","first-page":"D704","DOI":"10.1093\/nar\/gkz997","article-title":"The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species","volume":"48","author":"Shefchek","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021042623034897600_DMM046573C62","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1164\/rccm.201809-1626OC","article-title":"Complete tracheal ring deformity. a translational genomics approach to pathogenesis","volume":"200","author":"Sinner","year":"2019","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"2021042623034897600_DMM046573C63","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ydbio.2015.06.009","article-title":"Endodermal Wnt signaling is required for tracheal cartilage formation","volume":"405","author":"Snowball","year":"2015","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C75","doi-asserted-by":"publisher","author":"Sosic","year":"2003","DOI":"10.1016\/s0092-8674(03)00002-3"},{"key":"2021042623034897600_DMM046573C64","doi-asserted-by":"publisher","first-page":"E10615","DOI":"10.1073\/pnas.1811624115","article-title":"Evolutionarily conserved Tbx5-Wnt2\/2b pathway orchestrates cardiopulmonary development","volume":"115","author":"Steimle","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042623034897600_DMM046573C65","doi-asserted-by":"publisher","first-page":"e19153","DOI":"10.7554\/eLife.19153","article-title":"Cilia-mediated Hedgehog signaling controls form and function in the mammalian larynx","volume":"6","author":"Tabler","year":"2017","journal-title":"eLife"},{"key":"2021042623034897600_DMM046573C66","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1242\/dev.127.10.2227","article-title":"Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway","volume":"127","author":"Tada","year":"2000","journal-title":"Development"},{"key":"2021042623034897600_DMM046573C67","doi-asserted-by":"publisher","first-page":"e1007346","DOI":"10.1371\/journal.pgen.1007346","article-title":"Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions","volume":"14","author":"Tan","year":"2018","journal-title":"PLoS Genet."},{"key":"2021042623034897600_DMM046573C68","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1126\/science.1075620","article-title":"Progression of vertebrate limb development through SHH-mediated counteraction of GLI3","volume":"298","author":"te Welscher","year":"2002","journal-title":"Science"},{"key":"2021042623034897600_DMM046573C69","doi-asserted-by":"publisher","first-page":"bio048728","DOI":"10.1242\/bio.048728","article-title":"The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components","volume":"9","author":"Teramoto","year":"2020","journal-title":"Biol. Open"},{"key":"2021042623034897600_DMM046573C70","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.stem.2018.08.008","article-title":"Esophageal organoids from human pluripotent stem cells delineate Sox2 functions during esophageal specification","volume":"23","author":"Trisno","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2021042623034897600_DMM046573C71","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ydbio.2018.08.011","article-title":"FOXF1 transcription factor promotes lung morphogenesis by inducing cellular proliferation in fetal lung mesenchyme","volume":"443","author":"Ustiyan","year":"2018","journal-title":"Dev. Biol."},{"key":"2021042623034897600_DMM046573C72","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1101\/gad.1693008","article-title":"A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb","volume":"22","author":"Vokes","year":"2008","journal-title":"Genes Dev."},{"key":"2021042623034897600_DMM046573C73","doi-asserted-by":"publisher","first-page":"1900382","DOI":"10.1183\/13993003.00382-2019","article-title":"ERS statement on tracheomalacia and bronchomalacia in children","volume":"54","author":"Wallis","year":"2019","journal-title":"Eur. Respir. J."},{"key":"2021042623034897600_DMM046573C74","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.046573","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.046573\/1820887\/dmm046573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.046573\/1820887\/dmm046573.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T21:39:28Z","timestamp":1619473168000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/14\/2\/dmm046573\/223292\/Disruption-of-a-Hedgehog-Foxf1-Rspo2-signaling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":76,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.046573","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.11.198556","asserted-by":"object"}]},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]},"article-number":"dmm046573"}}