Developmental effects of the protein kinase inhibitor kenpaullone on the sea urchin embryo

Comp Biochem Physiol C Toxicol Pharmacol. 2018 Jan:204:36-44. doi: 10.1016/j.cbpc.2017.11.001. Epub 2017 Nov 10.

Abstract

The selection and validation of bioactive compounds require multiple approaches, including in-depth analyses of their biological activity in a whole-animal context. We exploited the sea urchin embryo in a rapid, medium-scale range screening to test the effects of the small synthetic kinase inhibitor kenpaullone. We show that sea urchin embryos specifically respond to this molecule depending on both dose and timing of administration. Phenotypic effects of kenpaullone are not immediately visible, since this molecule affects neither the fertilization nor the spatial arrangement of blastomeres at early developmental stages. Nevertheless, kenpaullone exposure from the beginning of embryogenesis profoundly perturbs specification, detachment from the epithelium, and migration of the primary mesenchyme cells, thus affecting the whole embryonic epithelial mesenchymal transition process. Our results reaffirm the sea urchin embryo as an excellent and sensitive in vivo system, which provides straightforward and rapid response to external stimuli.

Keywords: Embryonic development; Gene expression; Kenpaullone; Kinase inhibitor; Sea urchin.

MeSH terms

  • Animals
  • Benzazepines / chemistry
  • Benzazepines / pharmacology*
  • Embryo, Nonmammalian / drug effects*
  • Embryonic Development / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Paracentrotus / embryology*
  • Protein Kinase Inhibitors / pharmacology*

Substances

  • Benzazepines
  • Indoles
  • Protein Kinase Inhibitors
  • kenpaullone