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

Elife. 2017 Aug 23:6:e29145. doi: 10.7554/eLife.29145.

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.

Keywords: Akt; CAPE; developmental biology; melanocyte; neural crest; sox10; stem cells; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*

Substances

  • Caffeic Acids
  • Proto-Oncogene Proteins c-akt
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol