Hedgehog-FGF signaling axis patterns anterior mesoderm during gastrulation

Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15712-15723. doi: 10.1073/pnas.1914167117. Epub 2020 Jun 19.


The mechanisms used by embryos to pattern tissues across their axes has fascinated developmental biologists since the founding of embryology. Here, using single-cell technology, we interrogate complex patterning defects and define a Hedgehog (Hh)-fibroblast growth factor (FGF) signaling axis required for anterior mesoderm lineage development during gastrulation. Single-cell transcriptome analysis of Hh-deficient mesoderm revealed selective deficits in anterior mesoderm populations, culminating in defects to anterior embryonic structures, including the pharyngeal arches, heart, and anterior somites. Transcriptional profiling of Hh-deficient mesoderm during gastrulation revealed disruptions to both transcriptional patterning of the mesoderm and FGF signaling for mesoderm migration. Mesoderm-specific Fgf4/Fgf8 double-mutants recapitulated anterior mesoderm defects and Hh-dependent GLI transcription factors modulated enhancers at FGF gene loci. Cellular migration defects during gastrulation induced by Hh pathway antagonism were mitigated by the addition of FGF4 protein. These findings implicate a multicomponent signaling hierarchy activated by Hh ligands from the embryonic node and executed by FGF signals in nascent mesoderm to control anterior mesoderm patterning.

Keywords: FGF signaling; Hedgehog signaling; embryonic node; mesoderm; single-cell sequencing.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Lineage / genetics
  • Chick Embryo
  • Fibroblast Growth Factor 4 / genetics*
  • Fibroblast Growth Factor 8 / genetics*
  • Fibroblast Growth Factors / genetics
  • Gastrula / growth & development
  • Gastrula / metabolism
  • Gastrulation / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Hedgehog Proteins / genetics
  • Mesoderm / growth & development
  • Mesoderm / metabolism
  • Mice
  • Signal Transduction / genetics
  • Single-Cell Analysis
  • Transcriptome / genetics
  • Zinc Finger Protein GLI1 / genetics*


  • Fgf4 protein, mouse
  • Fgf8 protein, mouse
  • Fibroblast Growth Factor 4
  • Gli1 protein, mouse
  • Hedgehog Proteins
  • Shh protein, mouse
  • Zinc Finger Protein GLI1
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors