Document Detail


Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos.
MedLine Citation:
PMID:  20553902     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polo-like kinase 1 (Plk1) is central to cell division. Here, we report that Plk1 is critical for mitosis in the embryonic development of zebrafish. Using a combination of several cell biology tools, including single-cell live imaging applied to whole embryos, we show that Plk1 is essential for progression into mitosis during embryonic development. Plk1 morphant cells displayed mitotic infidelity, such as abnormal centrosomes, irregular spindle assembly, hypercondensed chromosomes, and a failure of chromosome arm separation. Consequently, depletion of Plk1 resulted in mitotic arrest and finally death by 6days post-fertilization. In comparison, Plk2 or Plk3 morphant embryos did not display any significant abnormalities. Treatment of embryos with the Plk1 inhibitor, BI 2536, caused a block in mitosis, which was more severe when used to treat plk1 morphants. Finally, using an assay to rescue the Plk1 morphant phenotype, we found that the kinase domain and PBD domains are both necessary for Plk1 function in zebrafish development. Our studies demonstrate that Plk1 is required for embryonic proliferation because its activity is crucial for mitotic integrity. Furthermore, our study suggests that zebrafish will be an efficient and economical in vivo system for the validation of anti-mitotic drugs.
Authors:
Kilhun Jeong; Jae-Yeon Jeong; Hae-Ock Lee; Eunhee Choi; Hyunsook Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-08
Journal Detail:
Title:  Developmental biology     Volume:  345     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-10     Completed Date:  2010-09-15     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34-48     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biological Sciences and Institute of Molecular Biology and Genetics, College of Natural Sciences, Seoul National University, 599, Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Korea.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Animals, Genetically Modified
Apoptosis
Cell Cycle Proteins / antagonists & inhibitors,  genetics*,  metabolism
Cell Proliferation
Chromosome Segregation / drug effects
Embryo, Nonmammalian / cytology,  embryology,  metabolism*
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Green Fluorescent Proteins / genetics,  metabolism
Histones / genetics,  metabolism
In Situ Hybridization
Kinetics
Microscopy, Video / methods
Mitosis / drug effects
Molecular Sequence Data
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  genetics*,  metabolism
Proto-Oncogene Proteins / antagonists & inhibitors,  genetics*,  metabolism
Pteridines / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Zebrafish / embryology,  genetics
Zebrafish Proteins / antagonists & inhibitors,  genetics*,  metabolism
Chemical
Reg. No./Substance:
0/BI 2536; 0/Cell Cycle Proteins; 0/Histones; 0/Proto-Oncogene Proteins; 0/Pteridines; 0/Zebrafish Proteins; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1

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


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