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| Status |
Public on Jul 09, 2014 |
| Title |
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by array
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| Summary |
Gene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder.
Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented to characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression and distribution, which control epiboly and gastrulation, were not affected. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol-exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol-treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.
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| Overall design |
Control vs. ethanol-treated zebrafish embryos that were treated from 2 to 8 hours postfertilization. Total RNA from control and ethanol-treated embryos were harvested at 8 hours postfertilization.
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| Contributor(s) |
Sarmah S, Muralidharan P, Curtis CL, McClintick JN, Buente BB, Holdgrafer DJ, Ogbeifun O, Olorungbounmi OC, Patino L, Lucas R, Gilbert S, Groninger ES, Arciero J, Edenberg HJ, Marrs JA |
| Citation(s) |
24167711, 32127575 |
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| Submission date |
Jun 27, 2013 |
| Last update date |
Mar 16, 2020 |
| Contact name |
James A Marrs |
| E-mail(s) |
jmarrs@iupui.edu
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| Organization name |
Indiana University-Purdue University Indianapolis
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| Department |
Biology
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| Lab |
SL328
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| Street address |
723 West Michigan Street
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| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (1) |
| GPL1319 |
[Zebrafish] Affymetrix Zebrafish Genome Array |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA209877 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48380_RAW.tar |
20.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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