Document Detail


Extensive apoptosis and abnormal morphogenesis in pro-caspase-3 transgenic zebrafish during development.
MedLine Citation:
PMID:  18515717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pro-apoptotic caspase-3 gene has been shown to have key functions in the execution of apoptosis (programmed cell death) in vertebrate cells. However, the central role of caspase-3 in morphogenesis during development remains unclear. In this study, transgenic zebrafish that overexpress full-length pro-caspase-3 were generated to determine the effects of caspase genes on vertebrate morphogenesis and stress tolerance. The enhanced expression of the full-length pro-caspase-3 cDNA induced extremely high levels of caspase activity and extensive apoptosis in the transgenic embryos, and 33-46% of F2 embyos in the transgenic lines exhibited some form of morphological abnormality. Pro-caspase-3 transgenic zebrafish exhibited abnormal morphogenesis in the eyes, notochord, heart and yolk sac, suggesting that enhanced processing of pro-caspase-3 triggers significant apoptotic responses in the specific target tissues that are undergoing morphogenesis during development. The transgenic fish had reduced eye size and showed degeneration of the retina, including the photoreceptor cell layers, whereas pigmentation and lens formation were not affected. In addition, heart failure due to a weakened heartbeat and reduced circulation was noted in the pro-caspase-3 transgenic embryos. The transgenic embryos were markedly sensitive to stress conditions, such as UV irradiation at 2 or 5 mJ cm(-2). On the other hand, caspase-3 deficiency through injection of antisense morpholino oligo into embryos repressed apoptosis and enhanced stress tolerance after UV irradiation. Therefore, the caspase-3-mediated pro-apoptotic signalling pathway and its activation play critical roles in the induction of apoptosis and stress tolerance during zebrafish embryogenesis.
Authors:
Michiaki Yamashita; Nanami Mizusawa; Misako Hojo; Takeshi Yabu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of experimental biology     Volume:  211     ISSN:  0022-0949     ISO Abbreviation:  J. Exp. Biol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-02     Completed Date:  2008-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1874-81     Citation Subset:  IM    
Affiliation:
National Research Institute of Fisheries Science, 2-12-4 Fukuura, Yokohama 236-8648, Japan. mic@affrc.go.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified / embryology*
Apoptosis / physiology*
Caspase 3 / metabolism*
DNA Primers / genetics
Embryo, Nonmammalian / physiology,  radiation effects
Gene Expression Regulation, Developmental / genetics,  physiology*
Green Fluorescent Proteins
In Situ Nick-End Labeling
Morphogenesis / physiology*
Oligonucleotides
Signal Transduction / physiology*
Ultraviolet Rays
Zebrafish / embryology*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Oligonucleotides; 147336-22-9/Green Fluorescent Proteins; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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