Citation | Distinguished for the development of elegant techniques for microsurgery of mammalian embryos, and for his major contributions thereby to knowledge of early mammalian development. His techniques were the first to make the mammalian blastocyst accessible to experimental manipulation. One involves dissection of blastocysts into their constituent tissues, followed by their reconstitution from isolated components of differing genotypes. Another involves injection of cells into the blastocyst, enabling the production of chimaeras from embryos of different species or developmental stages. Injection of only a single cell provides the possibility of clonal analysis in vivo of mammalian development. He has used the cell injection method in studies of X-chromosome inactivation and to assess the developmental potential of normal embryonic cells and the teratocarcinoma stem cells, and the blastocyst reconstruction method to show that proliferation of trophoblast cells is dependent on the inner cell mass. Taken collectively, his methods provide a powerful approach to the understanding of mechanisms of embryonic determination and differentiation including control of the cell cycle and gene action. His work has given the first reliable fate map of a mammalian embryo based on genetic markers, and has enabled appraisal of early determinative events. |