A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development
- Boston Children's Hospital, United States
- Washington University School of Medicine, United States
- Harvard Medical School, United States
- Koninklijke Nederlandse Akademie van Wetenschappen (KNAW), University Medical Center Utrecht, Netherlands
Abstract
The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation.
Data availability
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A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest developmentPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE95815).
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A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE75356).
Article and author information
Author details
Funding
National Institutes of Health (F31CA180313)
- Christie Ciarlo
Melanoma Research Alliance
- Leonard I Zon
Lawrence Ellison Foundation
- Leonard I Zon
Howard Hughes Medical Institute
- Leonard I Zon
National Institutes of Health (R01CA103846)
- Leonard I Zon
National Institutes of Health (RO3DE024490)
- Eric Liao
National Institutes of Health (K08AR061071)
- Charles K Kaufman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
Ethics
Animal experimentation: Zebrafish were maintained under standard protocols approved by the Boston Children's Hospital (BCH) Institutional Animal Care and Use Committee (IACUC) (protocol # 14-10-2789R).
Version history
- Received: May 31, 2017
- Accepted: August 8, 2017
- Accepted Manuscript published: August 23, 2017 (version 1)
- Version of Record published: September 14, 2017 (version 2)
Copyright
© 2017, Ciarlo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development
eLife 6:e29145.
https://doi.org/10.7554/eLife.29145
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