The POU Domain Protein SPG (pou2/Oct4) Is Essential for Endoderm Formation in Cooperation With the HMG Domain Protein Casanova

Dev Cell. 2004 Jan;6(1):91-101. doi: 10.1016/s1534-5807(03)00396-4.


The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and endoderm. Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack endodermal precursors. Cell transplantations show that spg acts in early endodermal precursors, and cas mRNA-injection into MZspg embryos does not restore endoderm development. spg and cas together are both necessary and sufficient to activate endoderm development, and stimulate expression of a sox17 promoter-luciferase reporter. Endoderm and mesoderm derive from a common origin, mesendoderm. We propose that Spg and Cas commit mesendodermal precursors to an endodermal fate. The joint control of endoderm formation by spg and cas suggests that the endodermal germlayer may be a tissue unit with distinct genetic control, thus adding genetic support to the germlayer concept in metazoan development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • DNA-Binding Proteins / genetics
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology*
  • Embryo, Nonmammalian / metabolism
  • Endoderm / cytology
  • Endoderm / metabolism*
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Male
  • Octamer Transcription Factor-3
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / pharmacology
  • SOX Transcription Factors
  • SOXF Transcription Factors
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins*
  • Zygote / cytology
  • Zygote / metabolism


  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Octamer Transcription Factor-3
  • Pou5f3 protein, zebrafish
  • RNA, Messenger
  • SOX Transcription Factors
  • SOXF Transcription Factors
  • Transcription Factors
  • Zebrafish Proteins
  • sox17 protein, zebrafish
  • sox32 protein, zebrafish