Wnt11 promotes cardiomyocyte development by caspase-mediated suppression of canonical Wnt signals

Mol Cell Biol. 2011 Jan;31(1):163-78. doi: 10.1128/MCB.01539-09. Epub 2010 Nov 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspases / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • DNA Probes / genetics
  • Female
  • Fetal Heart / cytology
  • Fetal Heart / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Mice
  • Mice, Transgenic
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism*
  • Pregnancy
  • Protein Stability
  • Signal Transduction
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • DNA Probes
  • Wnt Proteins
  • Wnt11 protein, mouse
  • beta Catenin
  • Casp3 protein, mouse
  • Casp8 protein, mouse
  • Caspase 3
  • Caspase 8
  • Caspases