Aberrant organ development leads to human congenital abnormalities. We are investigating the processes of normal organ development and attempting to uncover the events that go wrong resulting in birth defects. One field of interest is the development of the limbs. Each year a large number of infants are born with defects of the arms and/or legs and we are studying a subset which manifest extra fingers and toes. We have identified the genetic mutations that constitute the molecular basis for the defect and propose to investigate how these mutations give rise to hands and feet abnormalities. A second interest is in the region of the viscera that includes the stomach, pancreas, spleen and small intestine. These organs are under strict left/right instructions to grow to one side of the body cavity. When the process of left/right patterning is disrupted a number of abnormalities occur including cardiac and gastrointestinal defects and often congenital loss of the spleen. We propose to study the processes that control the genesis and the placement of these organs.