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*

(all 10)

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

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: phenethyl caffeate	14-19 somites	neural crest crestin expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	14-19 somites	neural crest dlx2a expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	14-19 somites	neural crest inka1a expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	14-19 somites	neural crest pax7a expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	14-19 somites	neural crest sox10 expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	Prim-5	pigment cell csf1ra expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	Prim-5	pigment cell dct expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	Prim-5	pigment cell mitfa expression decreased amount, abnormal	Fig. 2
WT	chemical treatment by environment: phenethyl caffeate	Long-pec	caudal fin curved, abnormal	Fig. 4
WT	chemical treatment by environment: phenethyl caffeate	Long-pec	melanocyte decreased amount, abnormal	Fig. 4

1 - 10 of 15

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
a9		Complex	mpv17
cz1705Tg	Tg(-3.5ubb:mCherry)	Transgenic Insertion
cz3334Tg	Tg(crestin:EGFP)	Transgenic Insertion
cz3336Tg	Tg2(crestin:EGFP)	Transgenic Insertion
hu1435		Point Mutation	ptenb
hu1864		Point Mutation	ptena
w2		Point Mutation	mitfa
w47Tg	Tg(mitfa:GFP)	Transgenic Insertion
zf220Tg	Tg(-4725sox10:EGFP)	Transgenic Insertion
zf393Tg	Tg(sox10:Kaede)	Transgenic Insertion

1 - 10 of 10

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Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP
Kaede	EFG	Kaede
mCherry	EFG	mCherry

Mapping

Ciarlo et al., 2017 ZDB-PUB-170824-9 PMID:28832322

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

Ciarlo et al., 2017

ZDB-PUB-170824-9
PMID:28832322