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Microbead Implantation in the Zebrafish Embryo
Published on: July 30, 2015
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.
Abstract:
FGF signaling plays a pivotal role in regulating cell movements and lineage induction during gastrulation. Here we identify 44 microRNAs that are expressed in the primitive streak region of gastrula stage chicken embryos. We show that the primary effect of FGF signaling on microRNA abundance is to negatively regulate the levels of miR-let-7b, -9, -19b, -107, -130b, and -218. LIN28B inhibits microRNA processing and is positively regulated by FGF signaling. Gain- and loss-of-function experiments show that LIN28B negatively regulates the expression of miR-19b, -130b, and let-7b, whereas negative modulation of miR-9, -107, and -218 appears to be independent of LIN28B function. Predicted mRNA targets of the FGF-regulated microRNAs are over-represented in serine/threonine and tyrosine kinase receptors, including ACVR1, ACVR2B, PDGFRA, TGFBR1, and TGFBR3. Luciferase assays show that these and other candidates are targeted by FGF-regulated microRNAs. PDGFRA, a receptor whose activity is required for cell migration through the primitive streak, is a target of miR-130b and -218 in vivo. These results identify a novel mechanism by which FGF signaling regulates gene expression by negatively modulating microRNA abundance through both LIN28B-dependent and LIN28B-independent pathways.
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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