Linked Life Data

21199655

Source:http://linkedlifedata.com/resource/pubmed/id/21199655

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-5-11
pubmed:abstractText
In zebrafish, ovulated oocytes are loaded with maternal estrogen receptor 2a (esr2a) mRNA which is spread as granular and filamentous structures throughout the central ooplasm and is promptly relocated inside the blastodisc area at the 1-cell stage (0.2h post-fertilization, hpf), as shown by in situ hybridization. This transcript is available for translation until its sharp decline from 4 to 8 hpf, being replaced by low levels of zygotic esr2a mRNA mainly localized in the head region and around the yolk sac from 24 hpf until hatching at 48 hpf. To test the functional role of the maternal esr2a mRNA, 1- or 2-cell embryos were injected with 10.3 ng each of morpholino (MO) to knockdown translation (MO2-esr2a) of both maternal and zygotic esr2a transcripts, with a missplicing MO (MO3-esr2a) to effectively block post-transcriptionally the zygotic transcript alone, and with a non-specific MO-control. Treatment with MO2-esr2a increased apoptosis in embryos, especially in the brain, and caused severe malformations in 63% of 1-5 dpf larvae, as compared to 10-11% in those treated with MO3-esr2a and MO-control. Defects included body growth delay with curved shape, persistent yolk sac with reduced sub-intestinal veins and swollen yolk extension, abnormal brain and splanchnocranium development, smaller eyes and otic vesicles, pericardial oedema, uninflated swim bladder and rudimentary caudal fin with aberrant circular swimming. Affected larvae could survive for only 12-14 days. The MO2-esr2a phenotype was rescued with co-injection of 30 pg/embryo of mutated zebrafish esr2a mRNA encoding the full length of Esr2a, but containing eight silent mutations in the region recognised by MO2-esr2a. A lower dosage (15 pg) failed to recover mortality and abnormality. Raising the dosage to 60 and 90 pg increased abnormality, but not mortality, whereas with 120 pg both mortality and abnormality worsened, indicating a strict quantitative requirement of Esr2a. Co-injection of an anti-p53 MO failed to rescue the MO2-esr2a phenotype, eliminating the possibility of off-target effects. Pangenomic microarray analysis revealed that 240 and 219 significantly expressed transcripts were up- and down-regulated, respectively, by maternal Esr2a protein deficiency in 8-hpf MO2-esr2a embryos. Also at 48 hpf, 162 and 120 presumably zygotic transcripts were up- and down-regulated, respectively, but only 18 were in common with each of the 8-hpf sets. In total, the transcripts from 705 genes were affected by Esr2a knockdown. These findings suggest the involvement of maternal esr2a mRNA, presumably transactivated by maternal 17?-estradiol stored in the oocyte from enveloping granulosa cells, in the epigenetic programming of zebrafish development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-6840
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-9
pubmed:meshHeading
pubmed-meshheading:21199655-Animals, pubmed-meshheading:21199655-Animals, Genetically Modified, pubmed-meshheading:21199655-Cartilage, pubmed-meshheading:21199655-Embryo, Nonmammalian, pubmed-meshheading:21199655-Epigenesis, Genetic, pubmed-meshheading:21199655-Gene Expression Profiling, pubmed-meshheading:21199655-Gene Expression Regulation, Developmental, pubmed-meshheading:21199655-Gene Knockdown Techniques, pubmed-meshheading:21199655-Larva, pubmed-meshheading:21199655-Microarray Analysis, pubmed-meshheading:21199655-Phenotype, pubmed-meshheading:21199655-RNA, Messenger, pubmed-meshheading:21199655-RNA, Messenger, Stored, pubmed-meshheading:21199655-Receptors, Estrogen, pubmed-meshheading:21199655-Validation Studies as Topic, pubmed-meshheading:21199655-Zebrafish, pubmed-meshheading:21199655-Zebrafish Proteins
pubmed:year
2011
pubmed:articleTitle
The knockdown of the maternal estrogen receptor 2a (esr2a) mRNA affects embryo transcript contents and larval development in zebrafish.
pubmed:affiliation
Comparative Endocrinology Laboratory, Department of Biology, University of Padova, Via U. Bassi 58/B, 35131 Padova, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't