PUBLICATION
Effects of Cyclin Dependent Kinase 9 inhibition on zebrafish larvae
- Authors
- Matrone, G., Mullins, J.J., Tucker, C.S., Denvir, M.A.
- ID
- ZDB-PUB-161008-8
- Date
- 2016
- Source
- Cell cycle (Georgetown, Tex.) 15(22): 3060-3069 (Journal)
- Registered Authors
- Mullins, John
- Keywords
- CDK9, flavopiridol, morpholino, pharmacology, phenotype, zebrafish
- MeSH Terms
-
- Cell Death/drug effects
- Immunohistochemistry
- Piperidines/pharmacology
- Zebrafish/embryology
- Zebrafish/growth & development*
- PubMed
- 27715402 Full text @ Cell Cycle
Abstract
CDK9 is a known regulator of cellular transcription, growth and proliferation. Small molecule inhibitors are currently being developed and assessed in clinical trials as anti-cancer drugs. The zebrafish embryo provides an ideal model to explore the effects of CDK9 inhibition in-vivo. This has not been adequately explored previously at the level of a whole organism. We have compared and contrasted the effects of pharmacological and molecular inhibition of CDK9 on somatic growth, apoptosis and cellular proliferation in zebrafish larvae between 0 to 120 hours post fertilisation (hpf) using flavopiridol, a selective CDK9 antagonist, and CDK9-targeting morpholino. We demonstrate that the inhibition of CDK9 diminishes cellular proliferation and increases apoptosis. Subsequently, it affects somatic growth and development of a number of key embryonic structures including the brain, heart, eye and blood vessels. For the first time, we have localized CDK9 at a subcellular level in whole-mounted larvae. This works shows, at a high-throughput level, that CDK9 clearly plays a fundamental role in early cellular growth and proliferation.
Genes / Markers
Figure Gallery (5 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping