Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells

Description

Abstract (English)

Unlike almost all cell types, which contain a centrosome made of a pair of centrioles organizing microtubules, multiciliated cells form more than a hundred centrioles, which are necessary for the growth of motile cilia and the efficient propulsion of physiological fluids. These centrioles are produced by highjacking cell cycle and centriole duplication programs. However, how the MCC progenitor handles such a massive number of centrioles to finally organize them in an apical basal body patch is unclear. Here, using new cellular models and high-resolution imaging techniques, we identify the microtubule network as the bandleader, and show how it orchestrates the process in space and in time. Organized by the pre-existing centrosome at the start of amplification, microtubules build a nest of centriolar components from which procentrioles emerge. When amplification is over, the centrosome's dominance is lost as new centrioles mature and become microtubule nucleators. Microtubules then drag all the centrioles to the nuclear membrane, assist their isotropic perinuclear disengagement and their subsequent collective apical migration. These results reveal that in brain MCC as in cycling cells, the same dynamics -from the centrosome to the cell pole via the nucleus- exists, is the result of a reflexive link between microtubules and the progressive maturation of new centrioles, and participates in the organized reshaping of the entire cytoplasm. On the other hand, new elements described in this work such as microtubule-driven organization of a nest, identification of a spatio-temporal progression of centriole growth and microtubule-assisted disengagement, may shed new light on the centriole duplication program.