Related Experiment Video
Updated: Jan 20, 2026
Visualization and Analysis of Pharyngeal Arch Arteries using Whole-mount Immunohistochemistry and 3D Reconstruction
Published on: March 31, 2020
Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th
Helen M Phillips1, Catherine A Stothard1, Wasay M Shaikh Qureshi1
1Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne NE1 3BZ, UK.
Insights
Pax9 deficiency causes heart defects by disrupting pharyngeal arch artery formation. Tbx1 and Pax9 interact in the pharyngeal endoderm to regulate cardiovascular development, crucial for preventing aortic arch abnormalities.
Area of Science:
- Developmental Biology
- Genetics
- Cardiovascular Science
Background:
- 22q11 deletion syndrome is linked to heart and aortic arch artery defects.
- TBX1 is a key gene implicated in these developmental abnormalities.
- PAX9 is expressed in pharyngeal endoderm and affected by TBX1 mutations.
Purpose of the Study:
- To investigate the role of Pax9 in cardiovascular development.
- To explore the genetic interaction between Tbx1 and Pax9.
- To identify the cellular site of Tbx1-Pax9 interaction.
Main Methods:
- Generation and analysis of Pax9-deficient mice.
- Transcriptome analysis to identify gene interactions.
- Utilizing a novel Pax9Cre allele for lineage tracing.
Main Results:
- Pax9-deficient mice exhibit complex cardiovascular malformations, including aortic arch artery defects.
- Tbx1 and Pax9 show functional interaction, with double heterozygotes having increased interrupted aortic arch.
- The pharyngeal endoderm is identified as the critical site for Tbx1-Pax9 genetic interaction.
Conclusions:
- Pax9 is essential for normal morphogenesis of the pharyngeal arch artery system.
- A Tbx1-Pax9 signaling pathway from the pharyngeal endoderm is required for proper cardiovascular development.
- This study reveals a novel genetic mechanism underlying congenital heart defects associated with 22q11 deletion syndrome.
Abstract:
Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome 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 that affect 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 with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system.
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