Wnt11 Promotes Cardiomyocyte Development by Caspase-Mediated Suppression of Canonical Wnt Signals

被引：65

作者：

Abdul-Ghani, Mohammad ^{[1
,2
]}

Dufort, Daniel ^{[3
]}

Stiles, Rebecca ^{[1
,2
]}

De Repentigny, Yves ^{[1
]}

Kothary, Rashmi ^{[1
,2
]}

Megeney, Lynn A. ^{[1
,2
]}

机构：

[1] Ottawa Hosp, Regenerat Med Program, Res Inst, Ottawa, ON K1H 8L6, Canada

[2] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada

[3] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Dept Obstet & Gynecol,Div Expt Med, Montreal, PQ H3A 1A1, Canada

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2011年 / 31卷 / 01期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

STEM-CELL DIFFERENTIATION; GLYCOGEN-SYNTHASE KINASE-3-BETA; EMBRYONAL CARCINOMA-CELLS; BETA-CATENIN; CARDIOVASCULAR PROGENITORS; CARDIAC-HYPERTROPHY; KINASE; 3-BETA; N-CADHERIN; PATHWAY; EXPRESSION;

D O I：

10.1128/MCB.01539-09

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Specification and early patterning of the vertebrate heart are dependent on both canonical and noncanonical wingless (Wnt) signal pathways. However, the impact of each Wnt pathway on the later stages of myocardial development and differentiation remains controversial. Here, we report that the components of each Wnt signal conduit are expressed in the developing and postnatal heart, yet canonical/β-catenin activity is restricted to nonmyocardial regions. Subsequently, we observed that noncanonical Wnt (Wnt11) enhanced myocyte differentiation while preventing stabilization of the β-catenin protein, suggesting active repression of canonical Wnt signals. Wnt11 stimulation was synonymous with activation of a caspase 3 signal cascade, while inhibition of caspase activity led to accumulation of β-catenin and a dramatic reduction in myocyte differentiation. Taken together, these results suggest that noncanonical Wnt signals promote myocyte maturation through caspase-mediated inhibition of β-catenin activity. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

引用

页码：163 / 178

页数：16

共 77 条

[1] Rehabilitation of a contract killer: Caspase-3 directs stem cell differentiation [J].