{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:59:26Z","timestamp":1788321566339,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0801154"],"award-info":[{"award-number":["G0801154"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The 22q11 deletion syndromes represent a spectrum of overlapping conditions including cardiac defects and craniofacial malformations. Amongst the craniofacial anomalies that are seen, cleft of the secondary palate is a common feature. Haploinsufficiency of<jats:styled-content style=\"fixed-case\">TBX<\/jats:styled-content>1 is believed to be a major contributor toward many of the developmental structural anomalies that occur in these syndromes, and targeted deletion of<jats:italic>Tbx1<\/jats:italic>in the mouse reproduces many of these malformations, including cleft palate. However, the cellular basis of this defect is only poorly understood. Here, palatal development in the absence of<jats:italic>Tbx1<\/jats:italic>has been analysed, focusing on cellular properties within the whole mesenchymal volume of the palatal shelves. Novel image analyses and data presentation tools were applied to quantify cell proliferation rates, including regions of elevated as well as reduced proliferation, and cell packing in the mesenchyme. Also, cell orientations (nucleus\u2013Golgi axis) were mapped as a potential marker of directional cell movement. Proliferation differed only subtly between wild\u2010type and mutant until embryonic day (E)15.5 when proliferation in the mutant was significantly lower.<jats:italic>Tbx1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>palatal shelves had slightly different cell packing than wild\u2010type, somewhat lower before elevation and higher at E15.5 when the wild\u2010type palate has elevated and fused. Cell orientation is biased towards the shelf distal edge in the mid\u2010palate of wild\u2010type embryos but is essentially random in the<jats:italic>Tbx1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mutant shelves, suggesting that polarised processes such as directed cell rearrangement might be causal for the cleft phenotype. The implications of these findings in the context of further understanding Tbx1 function during palatogenesis and of these methods for the more general analysis of genotype\u2013phenotype functional relationships are discussed.<\/jats:p>","DOI":"10.1111\/joa.12425","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T10:41:45Z","timestamp":1450780905000},"page":"464-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity"],"prefix":"10.1111","volume":"228","author":[{"given":"Lara J.","family":"Brock","sequence":"first","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Economou","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyn T.","family":"Cobourne","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6102-2620","authenticated-orcid":false,"given":"Jeremy B.A.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"AgostinelliC(2009)CircStats: Circular Statistics. 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