ZFIN ID: ZDB-PUB-100621-32
Inhibition of Plk1 induces mitotic infidelity and embryonic growth defects in developing zebrafish embryos
Jeong, K., Jeong, J.Y., Lee, H.O., Choi, E., and Lee, H.
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:
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Cell Cycle Proteins/antagonists & inhibitors
  • Cell Cycle Proteins/genetics*
  • Cell Cycle Proteins/metabolism
  • Cell Proliferation
  • Chromosome Segregation/drug effects
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Histones/genetics
  • Histones/metabolism
  • In Situ Hybridization
  • Kinetics
  • Microscopy, Video/methods
  • Mitosis/drug effects
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases/antagonists & inhibitors
  • Protein-Serine-Threonine Kinases/genetics*
  • Protein-Serine-Threonine Kinases/metabolism
  • Proto-Oncogene Proteins/antagonists & inhibitors
  • Proto-Oncogene Proteins/genetics*
  • Proto-Oncogene Proteins/metabolism
  • Pteridines/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 20553902 Full text @ Dev. Biol.
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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.
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