Post-transcriptional tuning of FGF signaling mediates neural crest induction

Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33305-33316. doi: 10.1073/pnas.2009997117. Epub 2020 Dec 21.

Abstract

Ectodermal patterning is required for the establishment of multiple components of the vertebrate body plan. Previous studies have demonstrated that precise combinations of extracellular signals induce distinct ectodermal cell populations, such as the neural crest and the neural plate. Yet, we still lack understanding of how the response to inductive signals is modulated to generate the proper transcriptional output in target cells. Here we show that posttranscriptional attenuation of fibroblast growth factor (FGF) signaling is essential for the establishment of the neural crest territory. We found that neural crest progenitors display elevated expression of DICER, which promotes enhanced maturation of a set of cell-type-specific miRNAs. These miRNAs collectively target components of the FGF signaling pathway, a central player in the process of neural induction in amniotes. Inactivation of this posttranscriptional circuit results in a fate switch, in which neural crest cells are converted into progenitors of the central nervous system. Thus, the posttranscriptional attenuation of signaling systems is a prerequisite for proper segregation of ectodermal cell types. These findings demonstrate how posttranscriptional repression may alter the activity of signaling systems to generate distinct spatial domains of progenitor cells.

Keywords: FGF signaling; ectoderm; miRNAs; neural crest; signaling systems.

Publication types

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

MeSH terms

  • Animals
  • Cell Lineage
  • Chick Embryo
  • Ectoderm / cytology
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Biological
  • Neural Crest / cytology
  • Neural Crest / metabolism*
  • Ribonuclease III / metabolism
  • Signal Transduction* / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription, Genetic*

Substances

  • MicroRNAs
  • Fibroblast Growth Factors
  • Ribonuclease III