The role of polycystic kidney disease 1 (Pkd1) in craniofacial skeletal development and response to mechanical stress

Mechanical stress is an important factor in modulating postnatal skeletal growth and development. To study the cellular responses that lead to functional adaptation in the craniofacial skeleton, a mouse midpalatal suture expansion model was developed and subsequent cellular and tissue responses were characterized. An expansive force across the midpalatal suture resulted in increased periosteal cell proliferation and differentiation into osteoblasts throughout the experimental period. As a result, new bone formation was observed in the expanded suture area. This model system has proven to be very efficient in studying the cellular behaviors leading to bone modeling/remodeling in response to mechanical stress. It has also allowed hypotheses of mechanotransduction in the craniofacial skeleton to be tested using genetically modified mouse strains. Polycystin 1 (Pkd1) has recently been proposed as mechanosensor in kidney epithelial cells in response to fluid flow. In this thesis, mice with targeted inactivation of Pkd1 in skeletal tissues were generated and analyzed. Pkd1-deficient mice exhibited a delay in intramembranous ossification of the skull, retarded postnatal growth of the cran