Alteration of gene expression by alcohol exposure at early neurulation

Feng Zhou, Qianqian Zhao, Yunlong Liu, Charles R. Goodlett, Tiebing Liang, Jeanette McClintick, Howard Edenberg, Lang Li

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background: We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables.Result: Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.Conclusion: This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

Original languageEnglish
Article number124
JournalBMC Genomics
Volume12
DOIs
StatePublished - Feb 21 2011

Fingerprint

Neurulation
Alcohols
Gene Expression
Neural Tube
Genes
Histones
Embryonic Structures
Neural Tube Defects
Microarray Analysis
Phenotype
Intercellular Signaling Peptides and Proteins
Cellular Retinol-Binding Proteins
Teratogenesis
Glycophorin
beta 2-Microglobulin
Aldehyde Dehydrogenase
Informatics
Ceruloplasmin
Forelimb
Hematopoiesis

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Alteration of gene expression by alcohol exposure at early neurulation. / Zhou, Feng; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R.; Liang, Tiebing; McClintick, Jeanette; Edenberg, Howard; Li, Lang.

In: BMC Genomics, Vol. 12, 124, 21.02.2011.

Research output: Contribution to journalArticle

Zhou, Feng ; Zhao, Qianqian ; Liu, Yunlong ; Goodlett, Charles R. ; Liang, Tiebing ; McClintick, Jeanette ; Edenberg, Howard ; Li, Lang. / Alteration of gene expression by alcohol exposure at early neurulation. In: BMC Genomics. 2011 ; Vol. 12.
@article{079ef3088c1c48eba3e9d4c9b1d8bc6e,
title = "Alteration of gene expression by alcohol exposure at early neurulation",
abstract = "Background: We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables.Result: Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.Conclusion: This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.",
author = "Feng Zhou and Qianqian Zhao and Yunlong Liu and Goodlett, {Charles R.} and Tiebing Liang and Jeanette McClintick and Howard Edenberg and Lang Li",
year = "2011",
month = "2",
day = "21",
doi = "10.1186/1471-2164-12-124",
language = "English",
volume = "12",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Alteration of gene expression by alcohol exposure at early neurulation

AU - Zhou, Feng

AU - Zhao, Qianqian

AU - Liu, Yunlong

AU - Goodlett, Charles R.

AU - Liang, Tiebing

AU - McClintick, Jeanette

AU - Edenberg, Howard

AU - Li, Lang

PY - 2011/2/21

Y1 - 2011/2/21

N2 - Background: We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables.Result: Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.Conclusion: This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

AB - Background: We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables.Result: Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos.Conclusion: This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

UR - http://www.scopus.com/inward/record.url?scp=79951697871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951697871&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-12-124

DO - 10.1186/1471-2164-12-124

M3 - Article

C2 - 21338521

AN - SCOPUS:79951697871

VL - 12

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

M1 - 124

ER -