Molecular & Developmental Biology
Tadashi Ohkubo(Assis. Prof.)
The body and tissues of the developing embryo are repeatedly divided into sub-regions specified by characteristic gene expression and morphology. The process that gives rise to these sub-regions along some defined pattern is called “pattern formation” or “patterning.” The most popular model to explain the patterning process is the “morphogen gradient and threshold” theory. Actually, many genetic results indicate that secreted signal proteins such as Wnt, BMP, and Hedgehog function as morphogens in many aspects of patterning processes. However, in spite of the accumulation of genetic evidence, the biochemical characteristics, including modification and higher order structure, of morphogens remain to be elucidated. Thus, one of our major goals is to reveal the real image of morphogens and the molecular mechanism underlying the formation of morphogen gradients, including the secretion and extracellular transport of these morphogens. We are examining these issues by focusing on Wnt proteins using several different approaches, including protein chemistry, genetics, and bio-imaging. In contrast, the segmental sub-regions of the paraxial mesoderm, or somites, appear not to be simply directed by the morphogen gradient and threshold, but by a unique mechanism proceeding periodically. Somites are sequentially generated in an anterior-to-posterior order by converting oscillatory gene expression into periodical structures. The molecular mechanism underlying this conversion and morphological segmentation, however, has not yet been fully understood. Thus, another goal of our current studies is to reveal the molecular mechanism of this unique mode of patterning that underlies the periodical and sequential sub-division in our bodies. In addition to somite segmentation, we also start to examine the development of pharyngeal arches, another segmental structure in vertebrates.
- R. Takada, Y. Satomi, T. Kurata, N. Ueno, S. Norioka, H. Kondoh, T. Takao & S. Takada: ”Monounsaturated fatty acid modification of Wnt proteins: Its role in Wnt secretion.” Dev. Cell 11, 791-801 (2006)
- Y. Yamaguchi, S. Yonemura & S. Takada:“Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse.” Development 133 4737-4748 (2006)
- A.* Kawamura, S.* Koshida, H. Hijikata, T. Sakaguchi, H. Kondoh & S.* Takada: "These two authors contributed equally to this work.) Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites." Genes Dev. 19, 1156-1161 (2005)
- A. Kawamura, S. Koshida, H. Hijikata, A. Ohbayashi, H. Kondoh & S. Takada: "Groucho-associated transcriptional repressor Ripply1 is required for proper transition from the presomitic mesoderm to somites." Dev. Cell 9 735-744 (2005)
- S. Koshida, Y. Kishimoto, H. Ustumi,T. Shimizu, M. Furutani-Seiki, H. Kondoh & S. Takada: "Integrine5-dependent Fibronectin accumulation for maintenance of somite boundaries in zebrafish embryos." Dev. Cell 8, 587-598 (2005)