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RESEARCH PRODUCT

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

Maria Di BernardoLetizia AnelloVincenzo Cavalieri

subject

0301 basic medicineSea urchinEmbryo NonmammalianIndolesPhysiologymedicine.drug_classHealth Toxicology and MutagenesisMesenchymeSettore BIO/11 - Biologia MolecolareContext (language use)ToxicologyBiochemistry03 medical and health sciencesbiology.animalBotanymedicineAnimalsEpithelial–mesenchymal transitionProtein Kinase InhibitorsSea urchinKinase inhibitorMolecular StructurebiologyEmbryogenesisGene Expression Regulation DevelopmentalCell BiologyGeneral MedicineBlastomereBenzazepinesProtein kinase inhibitorEmbryonic stem cellKenpaulloneCell biology030104 developmental biologymedicine.anatomical_structureEmbryonic developmentembryonic structuresParacentrotusGene expression

description

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.

https://doi.org/10.1016/j.cbpc.2017.11.001