Ventx factors function as Nanog-like guardians of developmental potential in Xenopus

PLoS One. 2012;7(5):e36855. doi: 10.1371/journal.pone.0036855. Epub 2012 May 14.

Abstract

Vertebrate development requires progressive commitment of embryonic cells into specific lineages through a continuum of signals that play off differentiation versus multipotency. In mammals, Nanog is a key transcription factor that maintains cellular pluripotency by controlling competence to respond to differentiation cues. Nanog orthologs are known in most vertebrates examined to date, but absent from the Anuran amphibian Xenopus. Interestingly, in silico analyses and literature scanning reveal that basal vertebrate ventral homeobox (ventxs) and mammalian Nanog factors share extensive structural, evolutionary and functional properties. Here, we reassess the role of ventx activity in Xenopus laevis embryos and demonstrate that they play an unanticipated role as guardians of high developmental potential during early development. Joint over-expression of Xenopus ventx1.2 and ventx2.1-b (ventx1/2) counteracts lineage commitment towards both dorsal and ventral fates and prevents msx1-induced ventralization. Furthermore, ventx1/2 inactivation leads to down-regulation of the multipotency marker oct91 and to premature differentiation of blastula cells. Finally, supporting the key role of ventx1/2 in the control of developmental potential during development, mouse Nanog (mNanog) expression specifically rescues embryonic axis formation in ventx1/2 deficient embryos. We conclude that during Xenopus development ventx1/2 activity, reminiscent of that of Nanog in mammalian embryos, controls the switch of early embryonic cells from uncommitted to committed states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Cell Differentiation
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • MSX1 Transcription Factor / genetics
  • MSX1 Transcription Factor / metabolism
  • Mice
  • Nanog Homeobox Protein
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*

Substances

  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • MSX1 protein, Xenopus
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Recombinant Proteins
  • Xenopus Proteins