Grant: CIHR Fellowship

How cells differentiate and acquire specific identities, organize in an orchestrated manner to generate an anatomical, fully functional organ remains an open question in developmental biology. A longstanding interest of our lab is endodermal development, and how the respiratory and digestive tract and their associated organs emerge. We have previously shown that at midgestation, cells of the endoderm acquire an organotypic identity, prior to the appearance of overt anatomical features. To understand the mechanisms that govern the formation of endodermal organs will require a collaborative effort to integrate high resolution imaging with single-cell genomic technologies, coupled with precision mouse genetics. Towards that end, I propose to (1) combine high-resolution imaging and single-cell genomics to generate a reference 3D atlas of the gut tube, and (2) interrogate mechanisms involved in the formation of foregut organs such as lungs, liver, and pancreas. The atlas will serve as a benchmark for comparison between embryos and allow spatial mapping of informative genes. Next, I will generate mutations in genes hypothesized to be involved in foregut development and assess whether organ formation is affected and how. This project will enhance our understanding of normal foregut development, a cornerstone for improving the understanding and treatment of congenital birth defects and age-onset diseases associated with this tissue and its organ derivatives.