Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling

J Mol Cell Biol. 2015 Oct;7(5):455-65. doi: 10.1093/jmcb/mjv030. Epub 2015 May 19.

Abstract

The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Here, we demonstrate that through brief inhibition of Nodal signaling in vitro, mouse embryonic stem cell (ESC)-derived epiblast stem cells (ESD-EpiSCs) could be committed to transient ectodermal progenitor populations, which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4, respectively. Mechanistic studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells. Furthermore, FGF-Erk signaling may also be alleviated during the generation of ectoderm-like cells. Thus, our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs, which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.

Keywords: BMP4; EpiSCs; FGF; Nodal; ectoderm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Cell Differentiation / physiology
  • Ectoderm / cytology*
  • Ectoderm / metabolism
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / metabolism*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Germ Layers / cytology*
  • Germ Layers / metabolism
  • Mice
  • Nodal Protein / genetics
  • Nodal Protein / metabolism
  • Pregnancy
  • Signal Transduction / physiology

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Nodal Protein