アクティブボード・２０１０年８月
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研究発表を行った学会；
・第４３回日本発生生物学会年会.
　２０１０年　６月２０日〜２３日（京都）

タイトル；Tsukushi is a Frizzled Ligand that Regulates the Proliferation of Retinal Progenitor Cells.
　
発表者；　太田　訓正　氏
　　　（熊本大学　大学院生命科学研究部　神経分化学分野）

Abstract；
Wnt signaling orchestrates multiple aspects of central nervous system development, including cell proliferation and cell fate choices. In chick retina, Wnt2b is expressed in both the surface ectoderm and the retinal pigmented epithelium at optic cup stage. Using a clonal assay in retinal re-aggregation cultures, along with overexpression studies, it was proposed that Wnt2b plays a role in the proliferation of retinal progenitor cells without cell differentiation (Kubo et al., 2005).
We have identified a BMP antagonist, Tsukushi (TSK), which is a soluble molecule containing 12 leucine-rich repeats and belongs to the Small Leucine-Rich Proteoglycan family (Ohta et al., 2004). TSK is expressed in the primitive streak and Hensen’s node during chick gastrulation and involved in their formation (Ohta et al., 2004; Ohta et al., 2006). TSK is also involved in the neural crest specification of Xenopus embryo by regulating BMP and Delta-1 activities at the boundary between the neural and the non-neural ectoderm (Kuriyama et al., 2006).
When Wnt2b was over-expressed into chick optic vesicle at stage 10, Wnt2b induced prolonged proliferation of retinal progenitor cells in vitro. However, when Wnt2b was co-over-expressed with TSK, which is also expressed in the marginal-most tip of the chick retina, the proliferative activity of Wnt2b was almost inhibited. Biochemical analyses showed that TSK functions as a Wnt signaling inhibitor by direct binding to Frizzled at the extracellular region. In the mouse retina, TSK is expressed in the ciliary body (CB) in which retinal stem/progenitor cells are located, and targeted disruption of TSK in mouse resulted in the expansion of the CB and an increase in the number of retinal spheres. Using gain- and loss-of function studies, we uncover a new crucial role for TSK in maintaining the growth and undifferentiated properties of retinal progenitor cells as a niche molecule.