FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step epithelial to mesenchymal transition

Development. 2017 Apr 15;144(8):1412-1424. doi: 10.1242/dev.143578. Epub 2017 Feb 27.

Abstract

Mesoderm induction begins during gastrulation. Recent evidence from several vertebrate species indicates that mesoderm induction continues after gastrulation in neuromesodermal progenitors (NMPs) within the posteriormost embryonic structure, the tailbud. It is unclear to what extent the molecular mechanisms of mesoderm induction are conserved between gastrula and post-gastrula stages of development. Fibroblast growth factor (FGF) signaling is required for mesoderm induction during gastrulation through positive transcriptional regulation of the T-box transcription factor brachyury We find in zebrafish that FGF is continuously required for paraxial mesoderm (PM) induction in post-gastrula NMPs. FGF signaling represses the NMP markers brachyury (ntla) and sox2 through regulation of tbx16 and msgn1, thereby committing cells to a PM fate. FGF-mediated PM induction in NMPs functions in tight coordination with canonical Wnt signaling during the epithelial to mesenchymal transition (EMT) from NMP to mesodermal progenitor. Wnt signaling initiates EMT, whereas FGF signaling terminates this event. Our results indicate that germ layer induction in the zebrafish tailbud is not a simple continuation of gastrulation events.

Keywords: EMT; FGF; Neuromesodermal progenitor; Tailbud; Wnt; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Epithelial-Mesenchymal Transition*
  • Fibroblast Growth Factors / metabolism*
  • Gastrula / metabolism
  • Imaging, Three-Dimensional
  • Mesoderm / cytology
  • Mesoderm / embryology*
  • Mesoderm / metabolism
  • Nervous System / cytology*
  • Nervous System / embryology*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • T-Box Domain Proteins
  • Tail / embryology*
  • Vimentin / chemistry
  • Vimentin / metabolism
  • Wnt Signaling Pathway*
  • Xenopus laevis / embryology
  • Zebrafish / embryology
  • Zebrafish Proteins

Substances

  • T-Box Domain Proteins
  • Vimentin
  • Zebrafish Proteins
  • tbx16 protein, zebrafish
  • Fibroblast Growth Factors