Genes Controlling Embryonic Development
Our laboratory studies genes important for embryonic development in mice, and the relation between mutations in these genes and both congenital and acquired human disease. Our analyses focus on the Notch pathway, an evolutionarily conserved cell communication and signaling system, and on genes of the Snail superfamily, which encode transcriptional repressor proteins.
We have created and analyzed numerous genetically engineered mouse models to understand the essential functions of individual components of these pathways. We have also generated mouse models for inherited human disease syndromes such as Alagille syndrome, and for common birth defects such as cleft palate, craniosynostosis, and congenital heart defects, such as outflow tract patterning defects and patent ductus arteriosus. Current areas of interest include the role of Notch ligands in cardiovascular development, and in skeletal muscle and mesenchymal stem cells.
Figure 1. Defects in embryonic development in Notch pathway mutant mice. In all panels, the control embryo is on the left, with the mutant on the right. A) Patent ductus arteriosus in Jag1 conditional mutant embryos. B) Rib and vertebral defects in Notch-regulated ankyrin repeat (Nrarp) mutant embryos. C) Defects in formation of sensory cells of the inner ear in Jag1 conditional mutant embryos. D) Kidney defects in Notch2 hypomorphic mutant embryos.