竹丸 憲一 （Department of Phamacology, The State University of New York at Stony Brook）

2009年03月26日(木) 16:00 より 17:30 まで

山手地区３号館２階共通セミナー室

分子発生学研究部門 高田 慎治 内線5241

Intracellular signaling mediated by the canonical Wnt/β-catenin pathway plays crucial roles in embryonic development, stem cell self-renewal and adult homeostasis. Perturbations in Wnt signaling have been implicated in a range of human diseases. Upon Wnt stimulation, the central component β-catenin translocates into the nucleus and functions as a co-activator by binding to Tcf/Lef transcription factors, leading to target gene expression.
We previously reported an evolutionarily conserved β-catenin antagonist termed Chibby (Cby). Cby physically interacts with β-catenin and represses its transcriptional activation potential. To investigate the function of Cby in vertebrates, we generated Cby-null (Cby^-/-) mice. Unexpectedly, these animals suffer from recurrent upper respiratory tract infections due to a complete absence of mucociliary transport activity, reminiscent of primary ciliary dyskinesia (PCD). Electron microscopic (EM) studies revealed the presence of poorly differentiated multi-ciliated cells with markedly fewer ciliary projections in the nasal epithelium of Cby^-/- mice, although their axonemal structure appears normal. In support of their phenotypes, Cby protein is localized at the base of cilia. Consistent with Cby being a negative regulator of β-catenin, expression of direct β-catenin target genes is significantly elevated in Cby^-/- nasal epithelium tissue compared to wild-type control.
Collectively, our data suggest that Cby is involved in proper formation/function of motile cilia, probably through regulation of β-catenin signaling.


(セミナーは日本語で行われます)