Fibroblast growth factor (FGF) signaling during gastrulation negatively modulates the abundance of microRNAs that

Alexander S Bobbs1, Aleksi V Saarela, Tatiana A Yatskievych

  • 1Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85724, USA.

Insights

Fibroblast Growth Factor (FGF) signaling regulates microRNA levels during embryonic gastrulation. FGF signaling impacts microRNA abundance via LIN28B-dependent and independent pathways, affecting gene expression.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Fibroblast Growth Factor (FGF) signaling is crucial for embryonic development, particularly during gastrulation, regulating cell movements and lineage specification.
  • MicroRNAs (miRNAs) are small non-coding RNAs that play significant roles in post-transcriptional gene regulation.

Purpose of the Study:

  • To investigate the impact of FGF signaling on microRNA expression during chicken embryo gastrulation.
  • To identify specific microRNAs regulated by FGF signaling and elucidate the underlying mechanisms, including the role of LIN28B.

Main Methods:

  • Identification of microRNAs in the primitive streak region of gastrula stage chicken embryos.
  • Analysis of FGF signaling's effect on microRNA abundance using gain- and loss-of-function experiments.
  • Luciferase assays to validate predicted mRNA targets of FGF-regulated microRNAs.

Main Results:

  • 44 microRNAs were identified in the primitive streak region.
  • FGF signaling negatively regulates the abundance of specific microRNAs (miR-let-7b, -9, -19b, -107, -130b, -218).
  • LIN28B, a known inhibitor of miRNA processing, is positively regulated by FGF signaling and mediates the regulation of some, but not all, FGF-responsive miRNAs.
  • Predicted targets of these miRNAs include key serine/threonine and tyrosine kinase receptors, such as PDGFRA, which is validated as a target of miR-130b and -218.

Conclusions:

  • FGF signaling regulates gene expression during gastrulation by modulating microRNA abundance through both LIN28B-dependent and LIN28B-independent pathways.
  • This regulatory mechanism provides novel insights into how FGF signaling controls developmental processes at the post-transcriptional level.

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