The embryonic intestine must rotate so that it shifts to the left side of the body. Failure to do so results in gut malrotation, a birth defect of abnormal gut rotation (occurs once in 500 live births). While malrotation predisposes babies to volvulus, a catastrophic strangulation of the intestine and its blood supply, its origin remains unknown. It has long been assumed that rotation is intrinsic to the tube itself; however, our research has shown that it is instead determined by cellular changes within the dorsal mesentery (DM) that suspends the gut. DM starts as a symmetrical structure but at a critical time the left side of the DM condenses while the right side expands causing the DM to deform and swing the gut leftward. This critical leftward bias determines gut chirality. Combined with the unique accessibility of the chicken egg, we established the DM as a powerful model system to define the fundamental genetic mechanisms through which gut correctly rotates. Our lab has been successful at identifying genes that are responsible for the left side of the DM. However, the mechanisms governing the right side remain entirely unknown and are the major goal of this proposal. Our work will reveal the genetic basis of gut malrotation and may ultimately improve diagnosis in neonate.