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開催日時:平成20年 7月 8日(火)14:00~15:00

講 師:太田 訓正 准教授

所   属:熊本大学大学院・医学薬学研究部・神経分化学

演 題:Tsukushi is a Frizzled4 ligand that&s_comma; in
competition with Wnt2b&s_comma; regulates the proliferation of retinal stem/
progenitor cells

概 要:太田先生はBMP antagonistとして

Wnt signalling orchestrates multiple aspects of central nervous
system development&s_comma; including cell proliferation and cell fate
choices. In chick retina&s_comma; Wnt2b is expressed in both the surface
ectoderm and the retinal pigmented epithelium at optic cup stage. At
later stage&s_comma; Wnt2b is expressed in the marginal-most tip of the
embryonic chick retina. Using a clonal assay in retinal re-
aggregation cultures&s_comma; along with overexpression studies&s_comma; it was
proposed that Wnt2b plays a role in the proliferation of retinal
progenitor cells without cell differentiation (Kubo et al.&s_comma; 2005).
We have identified a BMP antagonist&s_comma; Tsukushi (TSK)&s_comma; which is a
soluble molecule containing 12 leucine-rich repeats and belongs to
the Small Leucine-Rich Proteoglycan family (Ohta et al.&s_comma; 2004). TSK
is expressed in the primitive streak and Hensen’s node during
chick gastrulation and involved in their formation (Ohta et al.&s_comma;
2004; Ohta et al.&s_comma; 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.&s_comma; 2006). Further&s_comma; TSK contributes to germ
layer formation and patterning in Xenopus development by modulating
Xnr2&s_comma; FGF&s_comma; and BMP signalling (Morris et al.&s_comma; 2007).
When Wnt2b was over-expressed into chick optic vesicle at stage 10&s_comma;
Wnt2b induced prolonged proliferation of retinal progenitor cells in
vitro. However&s_comma; when Wnt2b was co-over-expressed with TSK&s_comma; which is
also expressed in the marginal-most tip of the chick retina&s_comma; the
proliferative activity of Wnt2b was almost inhibited. Biochemical
analyses showed that TSK functions as a Wnt signaling inhibitor by
direct binding to Frizzled4 at the extracellular region. In the mouse
retina&s_comma; TSK is expressed in the ciliary body (CB) in which retinal
stem/progenitor cells are located&s_comma; 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&s_comma;
we uncover a new crucial role for TSK in maintaining the growth and
undifferentiated properties of retinal stem/progenitor cells as a
niche molecule.

世話人: ○渡辺 すみ子、中内 啓光