HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts

Science. 2015 Jun 26;348(6242):aaa6071. doi: 10.1126/science.aaa6071.


Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Lineage / genetics
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Heart / embryology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism
  • Myoblasts, Cardiac / cytology
  • Myoblasts, Cardiac / metabolism*
  • Organogenesis / genetics*
  • Stem Cell Niche / genetics
  • Stem Cell Niche / physiology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Wnt Signaling Pathway / genetics*


  • Bone Morphogenetic Proteins
  • Homeodomain Proteins
  • Hop protein, mouse
  • Tumor Suppressor Proteins