Effects of Cyclin Dependent Kinase 9 inhibition on zebrafish larvae

Gianfranco Matrone, John J Mullins, Carl S Tucker, Martin A Denvir

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3060-3069
Number of pages10
JournalCell cycle (Georgetown, Tex.)
Volume15
Issue number22
DOIs
StatePublished - Nov 16 2016

Keywords

  • Animals
  • Bromodeoxyuridine
  • Cell Death
  • Cell Proliferation
  • Cyclin-Dependent Kinase 9
  • Embryo, Nonmammalian
  • Flavonoids
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Larva
  • Morpholinos
  • Phenotype
  • Piperidines
  • Protein Kinase Inhibitors
  • Survival Analysis
  • Zebrafish
  • Journal Article

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