Pharyngeal arch cell signalling in arch artery morphogenesis

Abnormalities of the aortic arch arteries, such as interrupted aortic arch (IAA), cause serious clinical problems including reduced life expectancy and death.

The arch arteries form from the pharyngeal arch arteries (PAA) within the pharyngeal arches but the genetics and tissue-specific interactions underlying their development is not fully understood. IAA is a hallmark of 22q11DS in which one of the deleted genes, TBX1, plays a crucial role.

We have shown that the pharyngeal endoderm is a key tissue in the morphogenesis of the PAA, as there is a strong and specific genetic interaction between Tbx1 and Pax9 in the pharyngeal endoderm for 4th PAA formation.

Deletion of Pax9 alone, which is expressed in the pharyngeal endoderm at mid-embryogenesis, leads to complex cardiovascular defects caused by aberrant morphogenesis of the PAA.

To uncover the gene regulatory networks and signalling events between the different cell types required for arch artery formation, we will employ single nuclei transcriptomics from human embryo and mouse wild-type and Tbx1;Pax9 mutant embryos.

This will enable us to identify the key genetic networks essential for PAA morphogenesis and to further our understanding into the normal biology underlying this process.