{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:27:35Z","timestamp":1789475255572,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Epigenetic and chromatin regulation of craniofacial development remains poorly understood. Ankyrin Repeat Domain 11 (<jats:italic>ANKRD11<\/jats:italic>) is a chromatin regulator that has previously been shown to control neural stem cell fates via modulation of histone acetylation. <jats:italic>ANKRD11<\/jats:italic> gene variants, or microdeletions of the 16q24.3 chromosomal region encompassing the <jats:italic>ANKRD11<\/jats:italic> gene, cause KBG syndrome, a rare autosomal dominant congenital disorder with variable neurodevelopmental and craniofacial involvement. Craniofacial abnormalities include a distinct facial gestalt, delayed bone age, tooth abnormalities, delayed fontanelle closure, and frequently cleft or submucosal palate. Despite this, the dramatic phenotype and precise role of <jats:italic>ANKRD11<\/jats:italic> in embryonic craniofacial development remain unexplored. Quantitative analysis of 3D images of KBG syndromic subjects shows an overall reduction in the size of the middle and lower face. Here, we report that mice with heterozygous deletion of <jats:italic>Ankrd11<\/jats:italic> in neural crest cells (Ankrd11<jats:sup>nchet<\/jats:sup>) display a mild midfacial hypoplasia including reduced midfacial width and a persistent open fontanelle, both of which mirror KBG syndrome patient facial phenotypes. Mice with a homozygous <jats:italic>Ankrd11<\/jats:italic> deletion in neural crest cells (Ankrd11<jats:sup>ncko<\/jats:sup>) die at birth. They show increased severity of several clinical manifestations described for KBG syndrome, such as cleft palate, retrognathia, midfacial hypoplasia, and reduced calvarial growth. At E14.5, <jats:italic>Ankrd11<\/jats:italic> expression in the craniofacial complex is closely associated with developing bony structures, while expression at birth is markedly decreased. Conditional deletion of <jats:italic>Ankrd11<\/jats:italic> leads to a reduction in ossification of midfacial bones, with several ossification centers failing to expand and\/or fuse. Intramembranous bones show features of delayed maturation, with bone remodeling severely curtailed at birth. Palatal shelves remain hypoplastic at all developmental stages, with a local reduction in proliferation at E13.5. Our study identifies <jats:italic>Ankrd11<\/jats:italic> as a critical regulator of intramembranous ossification and palate development and suggests that Ankrd11<jats:sup>nchet<\/jats:sup> and Ankrd11<jats:sup>ncko<\/jats:sup> mice may serve as pre-clinical models for KBG syndrome in humans.<\/jats:p>","DOI":"10.3389\/fcell.2021.645386","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T13:08:57Z","timestamp":1619701737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["The Chromatin Regulator Ankrd11 Controls Palate and Cranial Bone Development"],"prefix":"10.3389","volume":"9","author":[{"given":"Daniela Marta","family":"Roth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranidhi","family":"Baddam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vidal-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose David","family":"Aponte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Thea","family":"De Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devyn","family":"Godziuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne Eve Scovil","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Footz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan F.","family":"Schachter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean E.","family":"Egan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Hallgr\u00edmsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastassia","family":"Voronova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"B1","author":"Adams","year":"2020","journal-title":"geomorph: Geometric Morphometric Analyses of 2D\/3D Landmark Data."},{"key":"B2","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/joa.13332","article-title":"Histological and molecular characterization of the growing nasal septum in mice.","volume":"238","author":"Baddam","year":"2020","journal-title":"J. Anat."},{"key":"B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-1-61779-415-5_2","article-title":"osteoblast isolation from murine calvaria and long bones","author":"Bakker","year":"2012","journal-title":"Bone Research Protocols Methods in Molecular Biology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications.","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/s20113171","article-title":"Fully automatic landmarking of syndromic 3D facial surface scans using 2D Images.","volume":"20","author":"Bannister","year":"2020","journal-title":"Sensors"},{"key":"B6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1152\/physiolgenomics.00116.2007","article-title":"An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda.","volume":"32","author":"Barbaric","year":"2008","journal-title":"Physiol. Genomics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.stem.2010.10.009","article-title":"Epigenetic mechanisms that regulate cell identity.","volume":"7","author":"Barrero","year":"2010","journal-title":"Cell Stem Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.bone.2015.04.035","article-title":"Bone development.","volume":"80","author":"Berendsen","year":"2015","journal-title":"Bone"},{"key":"B9","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1109\/34.24792","article-title":"Principal warps: thin-plate splines and the decomposition of deformations.","volume":"11","author":"Bookstein","year":"1989","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"B10","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1093\/jmcb\/mjy087","article-title":"The role of p53 in developmental syndromes.","volume":"11","author":"Bowen","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41588-018-0054-7","article-title":"A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.","volume":"50","author":"Breslow","year":"2018","journal-title":"Nat. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1002\/ajmg.a.33727","article-title":"Craniofacial ciliopathies: a new classification for craniofacial disorders.","author":"Brugmann","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-6-32","article-title":"How is epigenetic information maintained through DNA replication?","volume":"6","author":"Budhavarapu","year":"2013","journal-title":"Epigenet. Chromatin"},{"key":"B14","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/joa.12365","article-title":"Analysis of human soft palate morphogenesis supports regional regulation of palatal fusion.","volume":"227","author":"Danescu","year":"2015","journal-title":"J. Anat."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/jdb6040031","article-title":"It\u2019s about time: ossification center formation in C57BL\/6 mice from E12\u2013E16.","volume":"6","author":"Flaherty","year":"2018","journal-title":"J. Dev. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.devcel.2014.11.031","article-title":"Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.","volume":"32","author":"Gallagher","year":"2015","journal-title":"Dev. Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Bone remodeling.","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1038\/s41436-020-0845-y","article-title":"Automated syndrome diagnosis by three-dimensional facial imaging.","volume":"22","author":"Hallgr\u00edmsson","year":"2020","journal-title":"Genet. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.ydbio.2010.12.021","article-title":"Epithelial Wnt\/\u03b2-catenin signaling regulates palatal shelf fusion through regulation of Tgf\u03b23 expression.","volume":"350","author":"He","year":"2011","journal-title":"Dev. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.devcel.2016.04.002","article-title":"Sp7\/osterix is restricted to bone-forming vertebrates where it acts as a Dlx Co-factor in osteoblast specification.","volume":"37","author":"Hojo","year":"2016","journal-title":"Dev. Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ydbio.2014.09.034","article-title":"Epigenetic regulation in neural crest development.","volume":"396","author":"Hu","year":"2014","journal-title":"Dev. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1007\/s11914-017-0391-y","article-title":"Epigenetics and bone remodeling.","volume":"15","author":"Husain","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1369\/jhc.2008.950527","article-title":"Matrix mineralization as a trigger for osteocyte maturation.","volume":"56","author":"Irie","year":"2008","journal-title":"J. Histochem. Cytochem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1267\/ahc.33.385","article-title":"The histochemical and cytochemical changes from formative to resorptive osteocytes.","volume":"33","author":"Irie","year":"2000","journal-title":"Acta Histochem. Cytochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1586\/1744666X.2015.994507","article-title":"Autoimmune disease in the epigenetic era: how has epigenetics changed our understanding of disease and how can we expect the field to evolve?","volume":"11","author":"Jeffries","year":"2015","journal-title":"Expert Rev. Clin. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/bdra.23320","article-title":"Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip and palate in the A\/WySn mouse strain.","volume":"100","author":"Juriloff","year":"2014","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/978-981-10-3233-2_6","article-title":"Roles of Runx2 in skeletal development","author":"Komori","year":"2017","journal-title":"RUNX Proteins in Development and Cancer Advances in Experimental Medicine and Biology"},{"key":"B29","first-page":"636","article-title":"The genetic basis of craniofacial and dental abnormalities.","volume":"121","author":"Kouskoura","year":"2011","journal-title":"Schweiz Monatsschr Zahnmed"},{"key":"B30","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1597\/07-134.1","article-title":"DNA methylation changes during cleft palate formation induced by retinoic acid in mice.","volume":"45","author":"Kuriyama","year":"2008","journal-title":"Cleft Palate Craniofac. J."},{"key":"B31","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":"B32","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1042\/BJ20071484","article-title":"Ankyrin repeats-containing cofactors interact with ADA3 and modulate its co-activator function.","volume":"413","author":"Li","year":"2008","journal-title":"Biochem. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3666","DOI":"10.1172\/JCI39832","article-title":"A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans.","volume":"119","author":"Li","year":"2009","journal-title":"J. Clin. Invest."},{"key":"B34","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1002\/ajmg.a.37842","article-title":"Clinical and genetic aspects of KBG syndrome.","volume":"170","author":"Low","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00698","article-title":"Mesenchymal Bmp7 controls onset of tooth mineralization: a novel way to regulate molar cusp shape.","volume":"11","author":"Malik","year":"2020","journal-title":"Front. Physiol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17081329","article-title":"Epigenetic mechanisms in bone biology and osteoporosis: can they drive therapeutic choices?","volume":"17","author":"Marini","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00412-015-0530-0","article-title":"Chromatin deregulation in disease.","volume":"125","author":"Mirabella","year":"2016","journal-title":"Chromosoma"},{"key":"B39","article-title":"KBG Syndrome","author":"Morel Swols","year":"2018","journal-title":"Gene Reviews"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2019.119062","article-title":"Primary cilia in murine palatal rugae development.","volume":"34","author":"Nakaniwa","year":"2019","journal-title":"Gene Expression Patterns"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1242\/jcs.026351","article-title":"Identification of ANKRD11 as a p53 coactivator.","volume":"121","author":"Neilsen","year":"2008","journal-title":"J. Cell Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1038\/ejhg.2014.253","article-title":"Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations.","volume":"23","author":"Ockeloen","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1080\/03008207.2016.1177037","article-title":"Epigenetic regulation of bone cells.","volume":"58","author":"Park-Min","year":"2017","journal-title":"Connect Tissue Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-1-4939-8997-3_2","article-title":"Isolation and generation of osteoblasts.","volume":"1914","author":"Perp\u00e9tuo","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B45","year":"2020","journal-title":"R"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1242\/dev.191213","article-title":"FaceBase 3: analytical tools and FAIR resources for craniofacial and dental research.","volume":"147","author":"Samuels","year":"2020","journal-title":"Development"},{"key":"B47","doi-asserted-by":"publisher","first-page":"568.e23","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism.","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/B978-0-12-810493-4.00011-0","article-title":"Chapter 9 - morpho and rvcg \u2013 shape analysis in R: R-Packages for geometric morphometrics, shape analysis and surface manipulations","author":"Schlager","year":"2017","journal-title":"Statistical Shape and Deformation Analysis"},{"key":"B49","doi-asserted-by":"publisher","first-page":"41998","DOI":"10.1074\/jbc.M403702200","article-title":"Histone deacetylase 3 Interacts with Runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation.","volume":"279","author":"Schroeder","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B50","author":"Schroeder","year":"1998","journal-title":"The Visualization Toolkit : An Object-Oriented Approach to 3D Graphics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"131","DOI":"10.2217\/epi.13.1","article-title":"Epigenetic regulation of Sox4 during palate development.","volume":"5","author":"Seelan","year":"2013","journal-title":"Epigenomics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1597\/16-124","article-title":"Epigenetics and orofacial clefts: a brief introduction.","volume":"55","author":"Sharp","year":"2018","journal-title":"Cleft Palate Craniofac. J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10163","article-title":"A conditional knockout resource for the genome-wide study of mouse gene function.","volume":"474","author":"Skarnes","year":"2011","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1210\/me.2014-1091","article-title":"The osteoblast to osteocyte transition: epigenetic changes and response to the vitamin D3 hormone.","volume":"28","author":"St John","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1002\/dvdy.23868","article-title":"Epigenetic landscape and miRNA involvement during neural crest development.","volume":"241","author":"Strobl-Mazzulla","year":"2012","journal-title":"Dev. Dyn."},{"key":"B56","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/j.1749-6632.2009.05243.x","article-title":"Osteocyte primary cilium and its role in bone mechanotransduction.","volume":"1192","author":"Temiyasathit","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.4673771","author":"Vidal-Garc\u00eda","year":"2021","journal-title":"morpho. Tools. GM v1.0.0: A Set of R Tools to Help With Geometric Morphometric Analyses of 3D Data"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2016.00035","article-title":"MINC 2.0: a flexible format for multi-modal images.","volume":"10","author":"Vincent","year":"2016","journal-title":"Front. Neuroinform."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36742-0","article-title":"Prickle1 regulates differentiation of frontal bone osteoblasts.","volume":"8","author":"Wan","year":"2018","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/jbmr.2381","article-title":"HDAC5 controls MEF2C-driven sclerostin expression in osteocytes.","volume":"30","author":"Wein","year":"2015","journal-title":"J. Bone Miner Res."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0498-x","article-title":"Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications.","volume":"9","author":"Wilfert","year":"2017","journal-title":"Genome Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"6267","DOI":"10.1093\/emboj\/cdg599","article-title":"Osteocyte control of bone formation via sclerostin, a novel BMP antagonist.","volume":"22","author":"Winkler","year":"2003","journal-title":"EMBO J."},{"key":"B63","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.ydbio.2009.03.021","article-title":"Hand2 is required in the epithelium for palatogenesis in mice.","volume":"330","author":"Xiong","year":"2009","journal-title":"Dev. Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.mod.2008.06.007","article-title":"Cell lineage in mammalian craniofacial mesenchyme.","volume":"125","author":"Yoshida","year":"2008","journal-title":"Mech. Dev."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.bbrc.2007.05.017","article-title":"Characterization of transcriptional regulatory domains of ankyrin repeat cofactor-1.","volume":"358","author":"Zhang","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B66","doi-asserted-by":"publisher","first-page":"33799","DOI":"10.1074\/jbc.M403997200","article-title":"Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B67","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1093\/jb\/mvv059","article-title":"Dynamic and distinct histone modifications of osteogenic genes during osteogenic differentiation.","volume":"158","author":"Zhang","year":"2015","journal-title":"J. Biochem."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.645386\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T13:09:05Z","timestamp":1619701745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.645386\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":67,"alternative-id":["10.3389\/fcell.2021.645386"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.645386","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]},"article-number":"645386"}}