PUBLICATION

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

Authors
Ciarlo, C., Kaufman, C.K., Kinikoglu, B., Michael, J., Yang, S., D Amato, C., Blokzijl-Franke, S., den Hertog, J., Schlaeger, T.M., Zhou, Y., Liao, E., Zon, L.I.
ID
ZDB-PUB-170824-9
Date
2017
Source
eLIFE   6: (Journal)
Registered Authors
den Hertog, Jeroen, Liao, Eric, Schlaeger, Thorsten, Zhou, Yi, Zon, Leonard I.
Keywords
developmental biology, stem cells, zebrafish
MeSH Terms
  • Animals
  • Caffeic Acids/metabolism
  • Cell Differentiation/drug effects*
  • Cell Movement/drug effects*
  • Neural Crest/embryology
  • Phenylethyl Alcohol/analogs & derivatives
  • Phenylethyl Alcohol/metabolism
  • Proto-Oncogene Proteins c-akt/metabolism*
  • Signal Transduction*
  • Zebrafish/embryology*
PubMed
28832322 Full text @ Elife
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes