{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:48:37Z","timestamp":1762674517798,"version":"3.41.2"},"reference-count":29,"publisher":"The Company of Biologists","issue":"16","license":[{"start":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T00:00:00Z","timestamp":1628985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R35 DE027550"],"award-info":[{"award-number":["R35 DE027550"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005237","name":"Helen Hay Whitney Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005237","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Proper function of the vertebrate skeleton requires the development of distinct articulating embryonic cartilages. Irx transcription factors are arranged in co-regulated clusters that are expressed in the developing skeletons of the face and appendages. IrxB cluster genes are required for the separation of toes in mice and formation of the hyoid joint in zebrafish, yet whether Irx genes have broader roles in skeletal development remains unclear. Here, we perform a comprehensive loss-of-function analysis of all 11 Irx genes in zebrafish. We uncover conserved requirements for IrxB genes in formation of the fish and mouse scapula. In the face, we find a requirement for IrxAb genes and irx7 in formation of anterior neural crest precursors of the jaw, and for IrxBa genes in formation of endodermal pouches and gill cartilages. We also observe extensive joint loss and cartilage fusions in animals with combinatorial losses of Irx clusters, with in vivo imaging revealing that at least some of these fusions arise through inappropriate chondrogenesis. Our analysis reveals diverse roles for Irx genes in the formation and later segmentation of the facial skeleton.<\/jats:p>","DOI":"10.1242\/dev.197244","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T09:49:47Z","timestamp":1627897787000},"source":"Crossref","is-referenced-by-count":9,"title":["A comprehensive series of Irx cluster mutants reveals diverse roles in facial cartilage development"],"prefix":"10.1242","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-6835","authenticated-orcid":false,"given":"D'Juan T.","family":"Farmer","sequence":"first","affiliation":[{"name":"Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Punam","family":"Patel","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachelle","family":"Choi","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-0026","authenticated-orcid":false,"given":"J. Gage","family":"Crump","sequence":"additional","affiliation":[{"name":"Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"2021081609453810200_DEV197244C1","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1523\/JNEUROSCI.14-06-03475.1994","article-title":"Combinatorial expression of three zebrafish genes related to distal- less: part of a homeobox gene code for the head","volume":"14","author":"Akimenko","year":"1994","journal-title":"J. Neurosci."},{"key":"2021081609453810200_DEV197244C2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ydbio.2006.12.025","article-title":"Defects in brain patterning and head morphogenesis in the mouse mutant Fused toes","volume":"304","author":"Anselme","year":"2007","journal-title":"Dev. Biol."},{"key":"2021081609453810200_DEV197244C3","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.devcel.2015.10.004","article-title":"Iroquois proteins promote skeletal joint formation by maintaining chondrocytes in an immature state","volume":"35","author":"Askary","year":"2015","journal-title":"Dev. Cell"},{"key":"2021081609453810200_DEV197244C4","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.1016\/j.cub.2017.11.022","article-title":"Vagus motor neuron topographic map determined by parallel mechanisms of hox5 expression and time of axon initiation","volume":"27","author":"Barsh","year":"2017","journal-title":"Curr. Biol."},{"key":"2021081609453810200_DEV197244C5","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/ng.2259","article-title":"Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1","volume":"44","author":"Bonnard","year":"2012","journal-title":"Nat. Genet."},{"key":"2021081609453810200_DEV197244C6","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.bonr.2016.02.005","article-title":"Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization","volume":"5","author":"Cain","year":"2016","journal-title":"Bone Rep."},{"key":"2021081609453810200_DEV197244C7","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1242\/dev.128.15.2847","article-title":"The Iroquois family of genes: from body building to neural patterning","volume":"128","author":"Cavodeassi","year":"2001","journal-title":"Development"},{"key":"2021081609453810200_DEV197244C8","doi-asserted-by":"publisher","first-page":"e1002938","DOI":"10.1371\/journal.pgen.1002938","article-title":"An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest","volume":"8","author":"Cox","year":"2012","journal-title":"PLoS Genet."},{"key":"2021081609453810200_DEV197244C9","doi-asserted-by":"publisher","first-page":"4457","DOI":"10.1242\/dev.129.19.4457","article-title":"Requirement for endoderm and FGF3 in ventral head skeleton formation","volume":"129","author":"David","year":"2002","journal-title":"Development"},{"key":"2021081609453810200_DEV197244C10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1471-213X-8-105","article-title":"An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10","volume":"8","author":"Dutton","year":"2008","journal-title":"BMC Dev. 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Biol."},{"key":"2021081609453810200_DEV197244C14","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nbt.2501","article-title":"Efficient genome editing in zebrafish using a CRISPR-Cas system","volume":"31","author":"Hwang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2021081609453810200_DEV197244C15","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1161\/CIRCRESAHA.112.265041","article-title":"Iroquois homeodomain transcription factors in heart development and function","volume":"110","author":"Kim","year":"2012","journal-title":"Circ. Res."},{"key":"2021081609453810200_DEV197244C16","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.devcel.2014.03.001","article-title":"Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling","volume":"29","author":"Li","year":"2014","journal-title":"Dev. 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