Use of small molecule inhibitors of the Wnt and Notch signaling pathways during Xenopus development

•XAV939 and IWR-1 are effective small molecule inhibitors of Wnt signaling.•BIO is an potent activator of Wnt signaling.•DAPT and RO4929097 are effective small molecule inhibitors of Notch signaling, but RO4929097 is the more potent reagent. Small molecule inhibitors of growth factor signaling pathw...

Full description

Saved in:
Bibliographic Details
Published in:Methods (San Diego, Calif.) Calif.), 2014-04, Vol.66 (3), p.380-389
Main Authors: Myers, Candace T., Appleby, Sarah C., Krieg, Paul A.
Format: Article
Language:English
Subjects:
Animals
Axin2
BIO
Body Patterning - drug effects
DAPT
Embryonic Development - drug effects
Embryonic Development - physiology
Hematopoeisis
Heterocyclic Compounds, 3-Ring - pharmacology
Imides - pharmacology
IWR-1
Notch
Quinolines - pharmacology
Receptors, Notch - metabolism
Receptors, Notch - physiology
RO4929097
Signal Transduction - drug effects
Wnt
Wnt Signaling Pathway - drug effects
Wnt Signaling Pathway - physiology
WntC59
XAV939
Xenopus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•XAV939 and IWR-1 are effective small molecule inhibitors of Wnt signaling.•BIO is an potent activator of Wnt signaling.•DAPT and RO4929097 are effective small molecule inhibitors of Notch signaling, but RO4929097 is the more potent reagent. Small molecule inhibitors of growth factor signaling pathways are extremely convenient reagents for investigation of embryonic development. The chemical may be introduced at a precise time, the dose can be altered over a large range and the chemical may be removed simply by replacing the medium surrounding the embryo. Because small molecule modulators are designed to target conserved features of a protein, they are usually effective across species. Ideally the chemicals offer remarkable specificity for a particular signaling pathway and exhibit negligible off-target effects. In this study we examine the use of small molecules to modulate the Wnt and Notch signaling pathways in the Xenopus embryo. We find that IWR-1 and XAV939 are effective inhibitors of the canonical Wnt signaling pathway while BIO is an excellent activator. For Notch signaling, we find that both DAPT and RO4929097 are effective inhibitors, but that RO4929097 is the more potent reagent. This report provides researchers with useful working concentrations of reagents and a small series of genetic and biological assays that may be used to characterize the role of Wnt and Notch signaling during embryonic development.
ISSN:1046-2023
1095-9130
DOI:10.1016/j.ymeth.2013.08.036