During morphogenesis of vertebrates, the embryonic body is gradually divided into sub-regions that are specified to give rise to functional units. Most of the processes are driven by the function of secreted signal proteins, or the morphogens, which are transmitted locally, presumably due to the tight control of their secretion and transport. We are currently examining the molecular mechanism underlying their secretion and transport by focusing on Wnt proteins. In contrast to the regionalization by the morphogens, the regionalization, or the segmentation, of somites is regulated by a different manner. Somites, which give rise to metameric structures such as the vertebrae of the axial skeleton, are sequentially generated in a rhythmic fashion at regular spatiotemporal intervals. To reveal the molecular mechanism by which periodical unit of somite is generated, we are characterizing genes involved in somite segmentation.
Figure 1: Wnt secretion pathway: Wnt proteins require specific machinery for their secretion. Wntless (Wls), a seven-pass membrane protein, is required for intracellular transport of Wnt proteins. After release of Wnt proteins into the extracellular space, Wls is recycled from the plasma membrane back to the Golgi apparatus by the retromer complex. Prior to the association with Wls, Wnt proteins are modified with a fatty acid, palmitoleoylate, by Porcupine in the ER.
Figure 2: Ripply1 and Ripply2 determine the positions of somite boundaries through degradation of Tbx6 proteins. In Ripply1/2-deficient mouse embryos, the anterior border of the Tbx6 domain is expanded anteriorly.
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Okubo, T., Kawamura, A.,Takahashi, J., Yagi, H., Morishima, M., Matsuoka, R., & Takada, S. (2011). Ripply3, a normal ofteries are likely to be generated Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice. Development 138, 339-348.
Kawamura, A., Koshida, S., & Takada, S. (2008). Activator-to-repressor conversion of T-box transcription factors by the Ripply family of Groucho/TLE-associated mediators. Mol Cell Biol. 28, 3236-3244.
Akanuma, T., Koshida, S., Kawamura, A., Kishimoto, Y., and Takada, S. (2007). Paf1 complex homologes are required for Notch-regulated transcription during somite segmentation. EMBO Rep. 8, 858-863
Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H. Takao, T., and Takada, S. (2006). Monounsaturated fatty acid modification of Wnt proteins: Its role in Wnt secretion. Dev. Cell 11, 791-801
Kawamura, A. Koshida, S., Hijikata, H., Sakaguchi, T., Kondoh, H., and Takada, S. (2005). Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. Genes Dev. 19, 1156-1161.
Koshida, S., Kishimoto, Y., Utsumi, H.,Shimizu, T., Furutani-Seiki, M., Kondoh, H., and Takada, S. (2005). Integrinα5-dependent fibronectin accumulation for maintenance of somite boundaries in zebrafish embryos. Dev. Cell 8, 587-598.
Professor TAKADA, Shinji TEL: +81 564 59 5241 E-mail: firstname.lastname@example.org