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A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599238/ https://www.ncbi.nlm.nih.gov/pubmed/28832322 http://dx.doi.org/10.7554/eLife.29145 |
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author | Ciarlo, Christie Kaufman, Charles K Kinikoglu, Beste Michael, Jonathan Yang, Song D′Amato, Christopher Blokzijl-Franke, Sasja den Hertog, Jeroen Schlaeger, Thorsten M Zhou, Yi Liao, Eric Zon, Leonard I |
author_facet | Ciarlo, Christie Kaufman, Charles K Kinikoglu, Beste Michael, Jonathan Yang, Song D′Amato, Christopher Blokzijl-Franke, Sasja den Hertog, Jeroen Schlaeger, Thorsten M Zhou, Yi Liao, Eric Zon, Leonard I |
author_sort | Ciarlo, Christie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5599238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55992382017-09-19 A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development Ciarlo, Christie Kaufman, Charles K Kinikoglu, Beste Michael, Jonathan Yang, Song D′Amato, Christopher Blokzijl-Franke, Sasja den Hertog, Jeroen Schlaeger, Thorsten M Zhou, Yi Liao, Eric Zon, Leonard I eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2017-08-23 /pmc/articles/PMC5599238/ /pubmed/28832322 http://dx.doi.org/10.7554/eLife.29145 Text en © 2017, Ciarlo et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Ciarlo, Christie Kaufman, Charles K Kinikoglu, Beste Michael, Jonathan Yang, Song D′Amato, Christopher Blokzijl-Franke, Sasja den Hertog, Jeroen Schlaeger, Thorsten M Zhou, Yi Liao, Eric Zon, Leonard I A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title | A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title_full | A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title_fullStr | A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title_full_unstemmed | A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title_short | A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development |
title_sort | chemical screen in zebrafish embryonic cells establishes that akt activation is required for neural crest development |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599238/ https://www.ncbi.nlm.nih.gov/pubmed/28832322 http://dx.doi.org/10.7554/eLife.29145 |
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