Understanding how genes control the shape and spatial orientation of organs is one of the goals of developmental biologists. In the mouse, as in other vertebrates, cells begin receiving and responding to instructions about their positional fate during the earliest stages of development, when the embryo resembles little more than a flat sheet of cells. The mice exhibited a number of developmental abnormalities, including inappropriate position of the heart and lungs. Humans with one defective copy of the Pitx2 gene have a constellation of problems called Rieger syndrome, the signs of which include irregularly shaped eyes, lack of tooth growth, craniofacial deformities, and, more rarely, problems with growth hormone production. Rosenfeld's team found that Pitx2 knockout mice had defective growth in their teeth and pituitary glands, the source of growth hormone.
Cell proliferation stops.
Once the Nodal signal arrives, it induces Pitx2 to help implement its directives. The results of earlier experiments that attempted to untangle the functions of Nodal and Pitx2 were intriguing, but did not produce a clear answer. When researchers added Nodal or Pitx2 to the right side of a mouse embryo, for example, the right side developed as a mirror image of the left. In other experiments, researchers added extra Nodal or Pitx2 to embryos only to find that the two proteins had similar effects. And knocking out the Nodal gene alone resulted in either mirror-image or randomized organization of multiple organs.