Pax9 regulation of extracellular matrix production in the pharyngeal endoderm (Ms Rebecca Steele)

The extracellular matrix (ECM) is a three-dimensional network of extracellular macromolecules that plays a vital role in embryonic development by providing structural and biochemical support, and signalling, to surrounding cells. Mice mutated for components of the ECM develop cardiovascular malformations.

Mice lacking the transcription factor Pax9, which is expressed in the pharyngeal endoderm at mid-embryogenesis, have complex cardiovascular defects affecting the formation of the aortic arch arteries concomitant with a reduction in neural crest cell (NCC) number within the pharyngeal arches. Importantly, NCC are known to interact with the ECM during migration.

However, it is not understood how signalling events from the endoderm can influence the cells required for arch artery morphogenesis derived from other germ layers, i.e the mesoderm for endothelial cells and the ectoderm for NCC.

RNA-seq analysis of Pax9-null pharyngeal arch tissue revealed that genes associated with the ECM were significantly differentially expressed. Pax9 may, therefore, regulate ECM gene expression in the pharyngeal endoderm.

This PhD project aims to identify how Pax9 potentially regulates ECM-related genes thereby providing a mechanism as to how signalling events from the pharyngeal endoderm may influence the development of the aortic arch arteries.