Show simple item record

dc.contributor.authorPhillips, Helen M.
dc.contributor.authorMaehr, Rene
dc.contributor.authorBamforth, Simon D.
dc.date2022-08-11T08:09:53.000
dc.date.accessioned2022-08-23T16:47:49Z
dc.date.available2022-08-23T16:47:49Z
dc.date.issued2019-08-23
dc.date.submitted2019-09-09
dc.identifier.citation<p>Development. 2019 Aug 23. pii: dev.177618. doi: 10.1242/dev.177618. [Epub ahead of print]. <a href="https://doi.org/10.1242/dev.177618">Link to article on publisher's site</a></p>
dc.identifier.issn0950-1991 (Linking)
dc.identifier.doi10.1242/dev.177618
dc.identifier.pmid31444215
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41155
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractDevelopmental 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31444215&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject22q11 deletion syndrome
dc.subjectArch artery development
dc.subjectNeural crest
dc.subjectPax9
dc.subjectPharyngeal endoderm
dc.subjectTbx1
dc.subjectCardiovascular System
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectDevelopmental Biology
dc.subjectEmbryonic Structures
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.titlePax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4(th) pharyngeal arch artery morphogenesis
dc.typeAccepted Manuscript
dc.source.journaltitleDevelopment (Cambridge, England)
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4960&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3944
dc.identifier.contextkey15291884
refterms.dateFOA2022-08-23T16:47:50Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3944
dc.contributor.departmentDiabetes Center of Excellence
dc.contributor.departmentProgram in Molecular Medicine


Files in this item

Thumbnail
Name:
dev.177618.full.pdf
Size:
3.384Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

© 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Except where otherwise noted, this item's license is described as © 2019. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.