The long-term goal of this proposal is to elucidate the molecular basis of patterning of the mesencephalon (midbrain) and metencephalon (cerebellum), jointly called mes-met. Embryological and genetic studies have indicated that Gbx2 and Otx2 play an important role in formation of an organizing center at the mes-met boundary, which directs development across the mes-met. These proposed studies are designed to further explore the function of Gbx2 and Otx2 in formation of the mid/hindbrain organizer. The first specific aim is to determine whether both Gbx2 and 01x2 are required to initiate the genetic cascade that regulates the formation of the mes-met organizer. The second specific aim is to determine the sequential roles of Gbx2 in establishment and maintenance of the mid/hindbrain organizer. Finally, the mechanisms of Gbx2 function in mid/hindbrain formation will be explored by chimeric analysis, in which behavior of Gbx2-deficient cells in the competition of wild-type cells, as well as expression of mes-met genes in these mutant cells will be analyzed.
