Abstract B26: Centriole amplification during mammalian multiciliated cell development reveals a novel centrosome asymmetry

Abstract

Abstract The centrosome comprises a mother and a daughter centriole, both regarded as equivalent in their ability to form new centrioles. Their symmetric duplication during the cell cycle is crucial for proper genetic partitioning between the daughter cells. In multiciliated cells, hundreds of centrioles are thought to appear de novo, i.e. independently from the centrosome, to nucleate the same number of motile cilia and propel physiological fluids. The origin of these centrioles remains unknown. Here we provide the cellular mechanism driving large-scale centriole production in multiciliated cells and identify the daughter centriole of the centrosome as the nucleation point for 95% of the new centrioles. Using live imaging combined with correlative super-resolution light and electron microscopy microscopy, we show that centriole amplification proceeds through a recurrent mechanism whereby the daughter centriole concomitantly generates the new centrioles and their cytoplasmic shuttles known as deuterosomes. By revealing this novel centrosome cycle, our work challenges the postulate that large-scale centriole production is a de novo mechanism in mammalian cells. In addition, it uncovers a fundamental asymmetry between mother and daughter centrioles in the control of centriole biogenesis and number. These results may have critical implications in the understanding of the etiology of cilia-related diseases, brain defects, and tumor formation. Citation Format: Adel Al Jord, Nathalie Spassky, Alice Meunier. Centriole amplification during mammalian multiciliated cell development reveals a novel centrosome asymmetry. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr B26.