Centriole Age Underlies Asynchronous Primary Cilium Growth in Mammalian Cells

Abstract

Summary Primary cilia are microtubule-based sensory organelles that are present in most mammalian tissues and play important roles in development and disease [1]. They are required for the Sonic hedgehog (Shh) [2-4] and PDGF [5] signalling pathways. Primary cilia grow from the older of the two centrioles of the centrosome, referred to as the mother centriole. In cycling cells the cilium typically grows in G1 and is lost before mitosis, but the regulation of its growth is poorly understood. Centriole duplication at G1/S results in two centrosomes, one with an older mother centriole and one with a new mother centriole, that are segregated in mitosis. We report that primary cilia grow asynchronously in sister cells resulting from a mitotic division, and that the sister cell receiving the older mother centriole usually grows a primary cilium first. We also show that the signaling proteins inversin [6] and PDGFRα localize asynchronously to sister cell primary cilia, and that sister cells respond asymmetrically to Sonic hedgehog. These results suggest that the segregation of differently aged mother centrioles, an asymmetry inherent to every animal cell division, can influence the ability of sister cells to respond to environmental signals, potentially altering the behavior or fate of one or both sister cells.