Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

Genes of the Hox family are critical for the proper development of the embryo as illustrated by the numerous congenital malformation associated with mutations in Hox genes. It is therefore critical to understand how these genes function. Previous work provided evidence that the Hox proteins act as pioneering factors, i.e. factors that can selectively open the chromatin allowing for differential gene activity. This differential gene activity is critical for the generation of different cell types in the developing embryo. The mechanism by which Hox proteins achieve this pioneering activity remains unknown. Using the mouse developing limb as a model system, we propose to identify this mechanism. Our work will help understanding the molecular basis of human congenital malformations associated with mutations in Hox genes.