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Particularly affected are the heart and great vessels, the endocrine glands of the neck, the face, the soft palate, and cognitive development. Although up to 50 genes may be deleted, it is haploinsufficiency of the transcription factor <jats:italic>TBX1<\/jats:italic> that is thought to make the greatest contribution to the disorder. Mouse embryos are exquisitely sensitive to varying levels of <jats:italic>Tbx1<\/jats:italic> mRNA, and <jats:italic>Tbx1<\/jats:italic> is required in all three germ layers of the embryonic pharyngeal region for normal development. TBX1 controls cell proliferation and affects cellular differentiation in a cell autonomous fashion, but it also directs non\u2010cell autonomous effects, most notably in the signaling between pharyngeal surface ectoderm and the rostral neural crest. TBX1 interacts with several signaling pathways, including fibroblast growth factor, retinoic acid, CTNNB1 (formerly known as <jats:italic>\u03b2<\/jats:italic>\u2010catenin), and bone morphogenetic protein (BMP), and may regulate pathways by both DNA\u2010binding and non\u2010binding activity. In addition to the structural abnormalities seen in 22q11 deletion syndrome (DS) and <jats:italic>Tbx1<\/jats:italic> mutant mouse models, patients reaching adolescence and adulthood have a predisposition to psychiatric illness. Whether this has a developmental basis and, if so, which genes are involved is an ongoing strand of research. Thus, knowledge of the genetic and developmental mechanisms underlying 22q11DS has the potential to inform about common disease as well as developmental defect. <jats:italic>WIREs Dev Biol<\/jats:italic> 2013, 2:393\u2013403. doi: 10.1002\/wdev.75<\/jats:p><jats:p>For further resources related to this article, please visit the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/wires.wiley.com\/remdoi.cgi?doi=10.1002\/wdev.75\">WIREs website<\/jats:ext-link>.<\/jats:p>","DOI":"10.1002\/wdev.75","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T16:56:37Z","timestamp":1340124997000},"page":"393-403","source":"Crossref","is-referenced-by-count":71,"title":["The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of 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