Our long-term goal is to understand the molecular bases controlling the differentiation and function of the osteoblasts, the bone-forming cells. Defects in osteoblast differentiation causes often invalidating or lethal skeletal dysplasia while impaired osteoblast function leads to bone loss and eventually to osteoporosis, one of the most common disease in the Western hemisphere. As of today, only few skeletal dysplasia have been correlated with mutation of a particular gene and anabolic treatments of bone loss are missing. Thus, our objective is to delineate the genetic bases regulating osteoblast biology to identify genes and pathways that could be used to diagnose, prevent and treat bone loss diseases. To identify factors controlling osteoblast differentiation and function we are using a combination of molecular biology and mouse genetics approaches. Our research effort is centered on two molecules known as critical regulators of osteoblast biology. First, we are developing a genome-wide screen to identify regulators of the expression and activity of Cbfa1, a transcription factor required for osteoblast differentiation during development that also controls the rate of bone formation during adulthood. Second, we are searching for modulators of the leptin pathway that was recently identified as one of the most powerful negative regulator of osteoblast function.