Document Detail

Conditional targeted cell ablation in zebrafish: a new tool for regeneration studies.
MedLine Citation:
PMID:  17326133     Owner:  NLM     Status:  MEDLINE    
Conditional targeted cell ablation in zebrafish would greatly expand the utility of this genetic model system in developmental and regeneration studies, given its extensive regenerative capabilities. Here, we show that, by combining chemical and genetic tools, one can ablate cells in a temporal- and spatial-specific manner in zebrafish larvae. For this purpose, we used the bacterial Nitroreductase (NTR) enzyme to convert the prodrug Metronidazole (Mtz) into a cytotoxic DNA cross-linking agent. To investigate the efficiency of this system, we targeted three different cell lineages in the heart, pancreas, and liver. Expression of the fusion protein Cyan Fluorescent Protein-NTR (CFP-NTR) under control of tissue-specific promoters allowed us to induce the death of cardiomyocytes, pancreatic beta-cells, and hepatocytes at specific times. Moreover, we have observed that Mtz can be efficiently washed away and that, upon Mtz withdrawal, the profoundly affected tissue can quickly recover. These findings show that the NTR/Mtz system is effective for temporally and spatially controlled cell ablation in zebrafish, thereby constituting a most promising genetic tool to analyze tissue interactions as well as the mechanisms underlying regeneration.
Silvia Curado; Ryan M Anderson; Benno Jungblut; Jeff Mumm; Eric Schroeter; Didier Y R Stainier
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental dynamics : an official publication of the American Association of Anatomists     Volume:  236     ISSN:  1058-8388     ISO Abbreviation:  Dev. Dyn.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-30     Completed Date:  2007-07-30     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1025-35     Citation Subset:  IM    
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MeSH Terms
Animals, Genetically Modified
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Genes, Transgenic, Suicide*
Genetic Engineering / methods*
Green Fluorescent Proteins / genetics,  metabolism
Heart / physiology
Hepatocytes / physiology
Insulin-Secreting Cells / physiology
Models, Biological
Myocardium / cytology
Myocytes, Cardiac / cytology
Nitroreductases / genetics,  metabolism
Organ Specificity / genetics
Promoter Regions, Genetic
Regeneration / physiology*
Zebrafish / embryology,  genetics,  physiology*
Grant Support
Reg. No./Substance:
0/Cyan Fluorescent Protein; 147336-22-9/Green Fluorescent Proteins; EC 1.7.-/Nitroreductases

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