Jeffrey, William IBN #9417799 Little is known about how changes in development arise during evolution. To address this problem, Dr. Jeffrey capitalizes on a unique model system consisting of closely-related species of ascidians with different forms of development. Ascidians are simple animals with many of the same developmental features as vertebrates, including a notochord (the evolutionary precursor of the vertebral column), a dorsal central nervous system, and a tail. Most ascidians develop the features described above, however, a few species have lost this property during evolution. One of the two species studied by this laboratory has vertebrate-like features, whereas the other has lost them. Remarkably, when these two species are hybridized, the species lacking vertebrate-like features recovers them, suggesting that the function of developmental regulatory genes has been lost in the latter species. This result opens the possibility of identifying genes involved in regulating development and evolution of the vertebrate-like features. Previously this laboratory has used a subtractive procedure in which the RNA products of cloned genes from one species were subtracted from those of another species to identify these regulatory genes. One of the genes the Jeffery group has identified is called manx because it is required for development of the tail (e.g. Manx cats lack a tail). The manx gene produces a regulatory protein that is likely to control the activity of other genes. This proposal will be funded in order to obtain more information on how the manx gene controls tail formation in ascidians and to identify the other genes controlled by manx that play a role in development of vertebrate-like features. Using these procedures, they will identify additional genes involved in development of the notochord, tail, and central nervous system. The information obtained is expected to help understand how the body plan is generated during the developm ent and evolution of higher animals.****