PUBLICATION
Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos
- Authors
- Jeong, K., Jeong, J.Y., Lee, H.O., Choi, E., and Lee, H.
- ID
- ZDB-PUB-100621-32
- Date
- 2010
- Source
- Developmental Biology 345(1): 34-48 (Journal)
- Registered Authors
- Lee, Hyunsook
- Keywords
- Zebrafish embryo, Plk1, Live-imaging, Prometaphase, Mitosis, BI 2536
- MeSH Terms
-
- Mitosis/drug effects
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Protein Serine-Threonine Kinases/antagonists & inhibitors
- Protein Serine-Threonine Kinases/genetics*
- Protein Serine-Threonine Kinases/metabolism
- Gene Expression Regulation, Developmental
- Molecular Sequence Data
- Microscopy, Video/methods
- Histones/genetics
- Histones/metabolism
- Sequence Homology, Amino Acid
- Pteridines/pharmacology
- Amino Acid Sequence
- Proto-Oncogene Proteins/antagonists & inhibitors
- Proto-Oncogene Proteins/genetics*
- Proto-Oncogene Proteins/metabolism
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Apoptosis
- Animals, Genetically Modified
- Chromosome Segregation/drug effects
- Cell Cycle Proteins/antagonists & inhibitors
- Cell Cycle Proteins/genetics*
- Cell Cycle Proteins/metabolism
- Cell Proliferation
- In Situ Hybridization
- Reverse Transcriptase Polymerase Chain Reaction
- Animals
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism*
- Gene Knockdown Techniques
- Kinetics
- PubMed
- 20553902 Full text @ Dev. Biol.
Citation
Jeong, K., Jeong, J.Y., Lee, H.O., Choi, E., and Lee, H. (2010) Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos. Developmental Biology. 345(1):34-48.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping