Wnt11 promotes cardiomyocyte development by caspase-mediated suppression of canonical Wnt signals.
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.
Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa Hospital, General Campus, Ottawa, Ontario K1H 8L6, Canada.
Mohammad
M
Abdul-Ghani
Daniel
D
Dufort
Rebecca
R
Stiles
Yves
Y
De Repentigny
Rashmi
R
Kothary
Lynn A
LA
Megeney
D000818:Animals; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D005260:Female; D005318:Fetal Heart / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D055550:Protein Stability; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D015342:DNA Probes; D051153:Wnt Proteins; C508957:Wnt11 protein, mouse; D051176:beta Catenin; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases