Elucidation of the chondrogenic gene regulatory network controlling embryonic skeletal development.

More than 90% of the skeleton in the developing mammalian embryo is formed via endochondral ossification which requires an obligatory cartilage intermediate as a template for bone formation, making chondrogenesis an essential pathway during development. Sox5, Sox6, and Sox9 were uncovered via classical genetic analyses of human diseases and mouse models to be the key transcription factors controlling chondrogenesis. The knowledge behind the regulation of the Sox proteins and the genes they regulate in vivo is still in its infancy. In this study by merging classical mouse genetics with advanced technology, transcriptome profiling and chromatin immunoprecipitation sequencing for the Sox trio were carried out in the mouse at E13.5 for the first time to gain insight to what is happening in the context of a developing embryo. From the analysis of the data generated, a novel high-confident chondrogenic gene regulatory network at E13.5 was built.​Doctor of Philosophy (SBS