UMMS Affiliation

Program in Molecular Medicine; Diabetes Center of Excellence

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Article Postprint


Cardiovascular System | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Developmental Biology | Embryonic Structures | Genetic Phenomena | Genetics and Genomics


Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in 22q11 deletion syndrome patients and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9 deficient mice are born with complex cardiovascular malformations affecting the outflow tract and aortic arch arteries with failure of the 3(rd) and 4(th) pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared to Tbx1 heterozygous mice. Using a novel Pax9Cre allele we demonstrated that the site of this Tbx1-Pax9 genetic interaction is in the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for critical tissue interactions during normal morphogenesis of the pharyngeal arch artery system.


22q11 deletion syndrome, Arch artery development, Neural crest, Pax9, Pharyngeal endoderm, Tbx1

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© 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

DOI of Published Version



Development. 2019 Aug 23. pii: dev.177618. doi: 10.1242/dev.177618. [Epub ahead of print]. Link to article on publisher's site

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Development (Cambridge, England)


Full author list omitted for brevity. For the full list of authors, see article.

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Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.