|New approaches to treating disease are set to revolutionise health care. Cancers will increasingly be treated by targeted molecules, not cytotoxic drugs. Manipulating stem cells for cell and tissue replacement therapies holds great promise for treatment of degenerative disease and injury. Both approaches depend critically on detailed knowledge of molecular and cellular events governing normal differentiation of target organs and tissues. This knowledge provides the basis for organ and tissue engineering. Very important life threatening or disabling diseases affect mesodermal organ systems. Heart failure and strokes resulting from atherosclerosis, kidney failure, muscular dystrophy, osteoporosis, tumours and leukaemia are caused either by defects in embryonic development of mesoderm containing organ systems or their function.. These diseases represent the principal obstacles to reaching a healthy old age. This proposal contributes to the knowledge base on which new diagnostic and therapeutic approaches will be based. We will elucidate molecular and cellular processes underlying embryonic specification and differentiation of mesodermal organs. It is clear that many developmental master genes later have key roles in regulating function and that cancers abusively reactivate developmental subroutines. We integrate established methodologies of developmental genetics and experimental embryology with sophisticated modern cell biology and new methodologies of genome scale analysis enabled by genome sequencing. The new technologies will reveal many genes which function in building a specific organ system or in directing a particular aspect of embryogenesis. Analysing these genes, investigating their functions, and placing them in developmental cascades as well as following the cells they affect, will reveal new aspects of organ development, extending and completing existing knowledge.