TBX3 Directs Cell-Fate Decision toward Mesendoderm

Stem Cell Reports. 2013 Aug 29;1(3):248-65. doi: 10.1016/j.stemcr.2013.08.002. eCollection 2013.


Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Embryonic Stem Cells / cytology*
  • Gastrulation / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Mesoderm / growth & development*
  • Mesoderm / metabolism
  • Mice
  • Nodal Protein / biosynthesis
  • Nodal Protein / genetics
  • Smad2 Protein / genetics
  • T-Box Domain Proteins / biosynthesis*
  • T-Box Domain Proteins / genetics
  • Xenopus


  • Nodal Protein
  • Nodal protein, mouse
  • Smad2 Protein
  • T-Box Domain Protein 2
  • T-Box Domain Proteins
  • Tbx3 protein, mouse