Dataset Information

Epithelial Wnt/?-catenin signaling regulates palatal shelf fusion through regulation of Tgf?3 expression.

ABSTRACT: The canonical Wnt/?-catenin signaling plays essential role in development and diseases. Previous studies have implicated the canonical Wnt/?-catenin signaling in the regulation of normal palate development, but functional Wnt/?-catenin signaling and its tissue-specific activities remain to be accurately elucidated. In this study, we show that functional Wnt/?-catenin signaling operates primarily in the palate epithelium, particularly in the medial edge epithelium (MEE) of the developing mouse palatal shelves, consistent with the expression patterns of ?-catenin and several Wnt ligands and receptors. Epithelial specific inactivation of ?-catenin by the K14-Cre transgenic allele abolishes the canonical Wnt signaling activity in the palatal epithelium and leads to an abnormal persistence of the medial edge seam (MES), ultimately causing a cleft palate formation, a phenotype resembling that in Tgf?3 mutant mice. Consistent with this phenotype is the down-regulation of Tgf?3 and suppression of apoptosis in the MEE of the ?-catenin mutant palatal shelves. Application of exogenous Tgf?3 to the mutant palatal shelves in organ culture rescues the midline seam phenotype. On the other hand, expression of stabilized ?-catenin in the palatal epithelium also disrupts normal palatogenesis by activating ectopic Tgf?3 expression in the palatal epithelium and causing an aberrant fusion between the palate shelf and mandible in addition to severely deformed palatal shelves. Collectively, our results demonstrate an essential role for Wnt/?-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgf?3 in the MEE.

SUBMITTER: He F

PROVIDER: S-EPMC3040240 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Epithelial Wnt/β-catenin signaling regulates palatal shelf fusion through regulation of Tgfβ3 expression.

He Fenglei F Xiong Wei W Wang Ying Y Li Lu L Liu Chao C Yamagami Takashi T Taketo Makoto M MM Zhou Chengji C Chen Yiping Y

Developmental biology 20101223 2

The canonical Wnt/β-catenin signaling plays essential role in development and diseases. Previous studies have implicated the canonical Wnt/β-catenin signaling in the regulation of normal palate development, but functional Wnt/β-catenin signaling and its tissue-specific activities remain to be accurately elucidated. In this study, we show that functional Wnt/β-catenin signaling operates primarily in the palate epithelium, particularly in the medial edge epithelium (MEE) of the developing mouse pa ...[more]

PMID: 21185284

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Project description:It has been suggested that drug tolerance represents a form of learning and memory, but this has not been experimentally established at the molecular level. We show that a component of alcohol molecular tolerance (channel internalization) from rat hippocampal neurons requires protein synthesis, in common with other forms of learning and memory. We identify ?-catenin as a primary necessary protein. Alcohol increases ?-catenin, and blocking accumulation of ?-catenin blocks alcohol-induced internalization in these neurons. In transfected HEK293 cells, suppression of Wnt/?-catenin signaling blocks ethanol-induced internalization. Conversely, activation of Wnt/?-catenin reduces BK current density. A point mutation in a putative glycogen synthase kinase phosophorylation site within the S10 region of BK blocks internalization, suggesting that Wnt/?-catenin directly regulates alcohol-induced BK internalization via glycogen synthase kinase phosphorylation. These findings establish de novo protein synthesis and Wnt/?-catenin signaling as critical in mediating a persistent form of BK molecular alcohol tolerance establishing a commonality with other forms of long-term plasticity.Alcohol tolerance is a key step toward escalating alcohol consumption and subsequent dependence. Our research aims to make significant contributions toward novel, therapeutic approaches to prevent and treat alcohol misuse by understanding the molecular mechanisms of alcohol tolerance. In our current study, we identify the role of a key regulatory pathway in alcohol-induced persistent molecular changes within the hippocampus. The canonical Wnt/?-catenin pathway regulates BK channel surface expression in a protein synthesis-dependent manner reminiscent of other forms of long-term hippocampal neuronal adaptations. This unique insight opens the possibility of using clinically tested drugs, targeting the Wnt/?-catenin pathway, for the novel use of preventing and treating alcohol dependency.

Dataset Information

Epithelial Wnt/?-catenin signaling regulates palatal shelf fusion through regulation of Tgf?3 expression.

Publications

Epithelial Wnt/β-catenin signaling regulates palatal shelf fusion through regulation of Tgfβ3 expression.

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