Endoderm Formation in Vertebrates


During vertebrate embryogenesis, endoderm, the inner‐most germ layer, will form the gut and associated organs, including liver and pancreas. Studies in the zebrafish, Xenopus and mouse have shown that the signalling pathways and transcription factors that regulate endodermal cell fate in the early embryo are largely conserved in vertebrates. Evidence from these model systems indicates Nodal signalling induces endoderm, in combination with the activity of transcription factors from the Mix, Gata, Sox and T‐box families. Other signalling pathways, such as Fgf, Bmp and Wnt, ensure the correct balance of mesoderm and endoderm is formed during gastrulation.

Key Concepts

  • Endoderm formation is initiated during mid‐blastula stages in zebrafish and Xenopus.
  • High levels of Nodal signalling induce endoderm formation.
  • A conserved set of transcription factors, of the Sox, Mix, Gata and T‐box families, act in a network with Nodal to establish endodermal fate during gastrulation.
  • The role of these factors and pathways downstream of Nodal signalling in early endoderm formation is mostly conserved; however, there are some species‐specific differences.
  • Other signalling pathways, notably the Fgf, Bmp and Wnt pathways, regulate the amount of endoderm that forms versus other germ layers.

Keywords: endoderm; Nodal; Sox; Gata; Mix; T‐box; network; conserved

Figure 1. Diagrams showing regions of each embryo that form mesoderm, endoderm and ectoderm. (a) Fate map of zebrafish at blastula stages. Cells in the tiers immediately overlying the yolk syncytial layer (YSL) are fated to become endoderm and mesoderm (mesendoderm; orange), cells in the tiers above these become mesoderm (red) and those of the animal region become ectoderm (blue). (b) Section through a Xenopus blastula showing a ring of mesoderm (red) in the equatorial region (marginal zone), the vegetal region that will form endoderm (yellow) and the animal region that will form ectodermal (blue) tissues. Some cells at the interface of the marginal zone and vegetal region will become endodermal or mesodermal (shown as orange). (c) Fate map of mouse embryo (simplified) at early streak stage showing the region of epiblast from which cells will form ectoderm (blue), mesoderm (red) and a mixture of mesoderm and endoderm (shown as orange). Unshaded regions are extra embryonic. Note that at borders between ectoderm/mesoderm/extraembryonic cells are mixed. PS: primitive streak.
Figure 2. Outcome of inhibiting or overexpressing Nodal in the zebrafish embryo. (a) Wildtype zebrafish embryo at 24 h post fertilisation (hpf). Lateral view. (b) Embryo with mutations in both maternal and zygotic tdgf1 (MZoep) at 24 hpf, showing lack of endoderm and most mesoderm. *Indicates remaining tail somites. Lateral view. (a,b) Courtesy of Tessa G. Montague. (c) In situ hybridisation of a wildtype zebrafish embryo at 5.3 hpf (50% epiboly) showing normal expression of foxa3, an endodermal marker gene, in the marginal zone of the embryo. Animal view. (d) In situ hybridisation of a zebrafish embryo at 5.3 hpf (50% epiboly) previously injected with ndr2 mRNA at the one cell stage, showing ectopic expression of foxa3 in the animal region of the embryo. Animal view. (c,d) Adapted from Nelson et al., .
Figure 3. Signals and transcription factors that regulate zebrafish endoderm formation. Mxtx2, a maternal factor, directly induces expression of ndr1 and ndr2 (nodals) in the YSL, which in turn induce nodals in the overlaying marginal zone cells, thus reinforcing nodal expression. Eomesa, another maternal factor expressed in the embryo, is also able to directly induce expression of nodals in the marginal zone. Nodals induce expression of gata5 and mixl1 at the margin, and these factors interact with Eomesa to directly induce expression of sox32. Sox32 in turn induces expression of sox17. sox17 marks cells that will form endodermal structures. Fgf and Bmp signalling inhibit the activity of Sox32, limiting the amount of endoderm formed in the embryo.


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Further Reading

Wlizla M and Zorn AM (2015) Vertebrate endoderm formation. In: Moody S (ed.) Principles of Developmental Genetics, pp 237–253.

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Wardle, Fiona C(Mar 2020) Endoderm Formation in Vertebrates. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028514]