RT Journal Article
SR Electronic
T1 <em>Pax9</em> is required for cardiovascular development and interacts with <em>Tbx1</em> in the pharyngeal endoderm to control 4<sup>th</sup> pharyngeal arch artery morphogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 576660
DO 10.1101/576660
A1 Helen M. Phillips
A1 Catherine A. Stothard
A1 Wasay Mohiuddin Shaikh Qureshi
A1 Anastasia I. Kousa
A1 J. Alberto Briones-Leon
A1 Ramada R. Khasawneh
A1 Rachel Sanders
A1 Silvia Mazzotta
A1 Rebecca Dodds
A1 Kerstin Seidel
A1 Timothy Bates
A1 Mitsushiro Nakatomi
A1 Simon J. Cockell
A1 Jürgen E. Schneider
A1 Timothy J. Mohun
A1 René Maehr
A1 Ralf Kist
A1 Heiko Peters
A1 Simon D. Bamforth
YR 2019
UL http://biorxiv.org/content/early/2019/03/14/576660.abstract
AB Developmental defects affecting the heart and aortic arch arteries are a key phenotype observed in DiGeorge syndrome patients and are caused by a microdeletion on chromosome 22q11. Heterozygosity of TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key component 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 3rd and 4th 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.Summary statement Pax9 is required for outflow tract and aortic arch development, and functions together with Tbx1 in the pharyngeal endoderm for 4th arch artery formation.