A gene regulatory program controlling early Xenopus mesendoderm formation: Network conservation and motifs

Semin Cell Dev Biol. 2017 Jun;66:12-24. doi: 10.1016/j.semcdb.2017.03.003. Epub 2017 Mar 22.


Germ layer formation is among the earliest differentiation events in metazoan embryos. In triploblasts, three germ layers are formed, among which the endoderm gives rise to the epithelial lining of the gut tube and associated organs including the liver, pancreas and lungs. In frogs (Xenopus), where early germ layer formation has been studied extensively, the process of endoderm specification involves the interplay of dozens of transcription factors. Here, we review the interactions between these factors, summarized in a transcriptional gene regulatory network (GRN). We highlight regulatory connections conserved between frog, fish, mouse, and human endodermal lineages. Especially prominent is the conserved role and regulatory targets of the Nodal signaling pathway and the T-box transcription factors, Vegt and Eomes. Additionally, we highlight network topologies and motifs, and speculate on their possible roles in development.

Keywords: Endoderm; Evolutionary conservation; Gene regulatory network; Network motifs; Transcription factors; Xenopus.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Endoderm / embryology*
  • Gene Regulatory Networks / genetics*
  • Transcription Factors / metabolism*
  • Xenopus / genetics*
  • Xenopus Proteins / genetics*


  • Transcription Factors
  • Xenopus Proteins