FK506-binding protein 5 regulates cell quiescence-proliferation decision in zebrafish epithelium.

Using a zebrafish ionocyte model, transcriptomics and genetic analyses were performed to identify pathways and genes involved in cell quiescence-proliferation regulation. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed that genes involved in transcription regulation, cell cycle, Foxo signalling and Wnt signalling pathway are enriched among the up-regulated genes while those involved in ion transport, cell adhesion and oxidation-reduction are enriched among the down-regulated genes. Among the top up-regulated genes is FK506-binding protein 5 (Fkbp5). Genetic deletion and pharmacological inhibition of Fkbp5 abolished ionocyte reactivation and impaired Akt signalling. Forced expression of a constitutively active form of Akt rescued the defects caused by Fkbp5 inhibition. These results uncover a key role of Fbkp5 in regulating the quiescence-proliferation decision via Akt signalling.