Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 0 |
Journal | Cell Cycle |
Early online date | 7 Oct 2016 |
DOIs | |
Publication status | E-pub ahead of print - 7 Oct 2016 |
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Martin Denvir
- Deanery of Clinical Sciences - Personal Chair of Medical Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active