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Molecular and Developmental Biology

  • Tsutomu Nohno, Ph.D.Professor

Emphasis and Outline of Education

Recent progress in human genome projects has facilitated great advances in medical care and technologies, such as gene diagnosis, gene therapy, and the regeneration of tissues and organs. To cope with advanced medical care, every physician is required to understand basic molecular mechanisms underlying biological processes in health and disease. In the Molecular Biology and Human Embryology courses, our students learn basic mechanisms of gene expression and signal transduction that account for cell-type specific proliferation and differentiation, and also acquire practical training in molecular biological techniques, including PCR (Polymerase Chain Reaction). Students are instructed on the molecular structure and function of genes and proteins, in addition to the molecular mechanisms underlying tumorigenesis and congenital disease.

Main Areas and Themes of Study

The aim of our research is to delineate the molecular basis of embryonic pattern formation and the mechanism of organogenesis that lead to the formation of tissues and organs from embryonic stem cells. Vertebrate limb development provides an experimental paradigm to investigate molecular mechanisms of pattern formation. Signaling centers are contained in the limb bud and determine spatial and temporal patterns during limb development. We have identified several signaling factors, such as members of the Wnt, Bmp and Fgf families, and their receptors. Recent studies have shown that these factors are produced locally within a specific region in the limb bud: Fgf4 and Fgf8 are produced in the AER that control limb outgrowth under the influence of Fgf10 produced in the limb mesoderm; Sonic hedgehog and Bmp2 are produced in the posterior limb bud called the ZPA that determines anterior-posterior limb pattern; and Wnt7a produced in the dorsal limb ectoderm instructs dorsal-ventral limb patterning. Current research efforts are continuing in an effort to determine precisely how these factors interact to impart positional information essential for final patterning of the limb. In addition to this research work, we are investigating limb regeneration in urodele amphibian. Newt and salamander are typical animals that can regenerate missing limb structures in adulthood. Master control genes regulating key events in morphogenesis are also used in the different systems including adult organs. Our efforts are directed towards delineating the mechanism of limb regeneration with a view to applying this knowledge to the regeneration of heart, kidney, pancreas, lung and other organs in mammals by controlling dedifferentiation and redifferentiation in a position-dependent manner.