Centriole amplification: High resolutive spatio-temporal dynamics and identification of regulators involved in asymmetric seeding at the centrosome – AsyMulti

Multiciliated cells (MCC) cover human epithelia to propel physiological fluids. A hallmark of their differentiation is the formation of up to 200 centrioles from which motile cilia are nucleated. Nonetheless, the mechanisms of their formation are still unidentified. Using a MCC culture assay, our recent results have shown that centrioles are amplified from the centrosomal daughter centriole revealing a new asymmetry between centrosomal centrioles. We will use a multidisciplinary approach to decipher this asymmetry. Through state of the art imaging techniques we will provide the 3D description of the amplification process. In parallel, a functional approach combining siRNA screen, ectopic protein expression, laser ablation and videomicroscopy will be run to determine the mechanisms underlying the asymmetry. Proteins identified by our study will constitute new potential targets to prevent cilia-related diseases and to circumvent pathological centriole amplification in cycling cells associated with microcephaly and cancer.