Abstract
Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of 22q11 deleted in humans with DiGeorge or velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that recapitulate major features of the syndrome, notably abnormal growth and remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency phenotype is modified by genetic background and by mutations in putative downstream targets. Homozygous null mutations of Tbx1 have more severe defects including failure of outflow tract septation, and absence of the caudal pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity has been linked to alterations in the expression of various genes involved in cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are dysregulated in Tbx1 mutants. This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control.
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The BHF and EU Framework 7 Programme EuroGeNet provided generous support.
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British Heart Foundation; EU Framework 7: CardioGeNet.
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Scambler, P.J. 22q11 Deletion Syndrome: A Role for TBX1 in Pharyngeal and Cardiovascular Development. Pediatr Cardiol 31, 378–390 (2010). https://doi.org/10.1007/s00246-009-9613-0
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DOI: https://doi.org/10.1007/s00246-009-9613-0