9728287 TURNBULL A persistent question in developmental neurobiology is when and how neuronal cells become committed to become particular cell types. Transplantation of cells and tissues from one region of the embryonic brain to another provides a method to test whether neural cells take on the characteristics of their new environment, or maintain the characteristics of their region of origin. In the past, these methods have been used in chick embryos, which are relatively easily accessible at embryonic stages. These studies have shown that tissue grafts from the mid-hindbrain, or early stage brainstem region maintain characteristics of the mid-hindbrain even after transplantation to far removed regions of the embryonic forebrain. Testing the commitment of mammalian neural cells through transplantation has been more difficult, because of the inaccessibility of embryos encased in the maternal uterus. Dr. Turnbull has recently developed a high resolution ultrasound imaging system which allows in utero image-guided transplantation of early stage neural cells between specific regions of the embryonic mouse brain. Using this system to transplant cells between embryonic mid-hindbrain and forebrain regions, Dr. Turnbull's laboratory has determined that a subpopulation of mouse mid-hindbrain cells are capable of taking on characteristics of the forebrain after transplantation, at embryonic stages significantly later than would have been predicted from previous experiments in the chick. Dr. Turnbull and his coworkers will now use this approach to characterize the embryonic stages at which cells from the mouse midbrain and cerebellum become committed to a mid-hindbrain fate. In addition, transplantation experiments will be conducted using neural cells from mouse mutant strains, in which alterations in specific genes are known to disrupt normal development of the early mid-hindbrain region. By comparing ultimate fates of transplanted normal cells versus cells obtained from defined mutant m ouse strains, these investigators will determine the role of several genes in committing mid-hindbrain cells to the fate of their region of origin. The experimental techniques being developed in this project, combining direct embryonic manipulations with the extensive genetic information and defined mutant strains available in the mouse, will provide a powerful new approach for studying developmental processes and genetic interactions in the mammalian nervous system.
