Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs

Cell Stem Cell. 2008 Jul 3;3(1):55-68. doi: 10.1016/j.stem.2008.04.004.


Wnt signaling is required for development of mesoderm-derived lineages and expression of transcription factors associated with the primitive streak. In a functional screen, we examined the mesoderm-inducing capacity of transcription factors whose expression was Wnt-dependent in differentiating ESCs. In contrast to many inactive factors, we found that mesoderm posterior 1 (Mesp1) promoted mesoderm development independently of Wnt signaling. Transient Mesp1 expression in ESCs promotes changes associated with epithelial-mesenchymal transition (EMT) and induction of Snai1, consistent with a role in gastrulation. Mesp1 expression also restricted the potential fates derived from ESCs, generating mesoderm progenitors with cardiovascular, but not hematopoietic, potential. Thus, in addition to its effects on EMT, Mesp1 may be capable of generating the recently identified multipotent cardiovascular progenitor from ESCs in vitro.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cardiovascular System / cytology*
  • Cell Differentiation / drug effects
  • Doxycycline / pharmacology
  • Embryonic Stem Cells / cytology*
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Gene Expression Regulation, Developmental
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Knockout
  • Wnt Proteins / physiology


  • Basic Helix-Loop-Helix Transcription Factors
  • Mesp1 protein, mouse
  • Wnt Proteins
  • Doxycycline