Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis

Autor: Anastasia I. Kousa, Catherine A. Stothard, Ralf Kist, Helen M. Phillips, J. Alberto Briones-Leon, Kerstin Seidel, Timothy Bates, Timothy J. Mohun, René Maehr, Mitsushiro Nakatomi, Rebecca Dodds, Simon Cockell, Rachel Sanders, Heiko Peters, Wasay Mohiuddin Shaikh Qureshi, Ramada R. Khasawneh, Simon D. Bamforth, Jürgen E. Schneider, Silvia Mazzotta
Jazyk: angličtina
Rok vydání: 2019
Předmět:
DOI: 10.1101/576660
Popis: 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 ofTBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key component for the arch artery defects.Pax9is expressed in the pharyngeal endoderm and is downregulated inTbx1mutant mice. We show here thatPax9deficient mice are born with complex cardiovascular malformations affecting the outflow tract and aortic arch arteries with failure of the 3rdand 4thpharyngeal arch arteries to form correctly. Transcriptome analysis indicated thatPax9andTbx1may function together, and mice double heterozygous forTbx1/Pax9presented with a significantly increased incidence of interrupted aortic arch when compared toTbx1heterozygous mice. Using a novelPax9Creallele we demonstrated that the site of thisTbx1-Pax9genetic interaction is in the pharyngeal endoderm, therefore revealing that aTbx1/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 statementPax9is required for outflow tract and aortic arch development, and functions together withTbx1in the pharyngeal endoderm for 4tharch artery formation.
Databáze: OpenAIRE