Centrosome in Cell Division, Development and Disease

Abstract The centrosome is a non‐membrane‐bound organelle present in most animal cells and it functions as the major microtubule‐organising centre (MTOC). Recent findings have revealed the detailed molecular and structural features of the centrosome, and architectural and functional changes at the centrosome during the cell cycle. The centriole, the organisational heart of the centrosome, duplicates once each cell cycle and depends on a hierarchy of regulatory and assembly factors for its biogenesis. The centrosome plays important roles in dividing and nondividing cells. This importance is reflected in the appearance of several human developmental disorders when genes encoding centrosomal proteins are mutated. The centriole is essential for the formation of cilia, the cell's ‘antennae’ that receive and transmit signals and sensory inputs critical for animal development and physiology. Impairment of cilium structure or function leads to a spectrum of diseases called ciliopathies. Key Concepts The centrosome typically contains a centriole pair, the mother and its daughter, and the pericentriolar material (PCM). Centrioles have a ninefold radial symmetry and are required for organising a functional centrosome. The PCM is a large multi‐protein complex that regulates microtubule (MT) assembly at centrosomes in dividing and nondividing cells. Centrioles duplicate only once each cell cycle, and the protein kinase PLK4 is a key early regulator of centriole duplication and biogenesis. The cartwheel at the proximal end of the centriole is assembled early in centriole biogenesis, and its ninefold symmetry is determined by the intrinsic properties of the key structural protein Sas‐6. The centrosome is involved in the asymmetric division of stem cells. In nondividing cells, the basal body, a modified mother centriole, serves as a platform for organising the MT‐based axoneme, forming a primary or motile cilium. Most vertebrate cells contain a primary cilium that is critical for signalling pathways including Hedgehog (Hh) signalling and left–right asymmetry designation during development. Centrosomal and ciliary dysfunctions have been linked to two types of diseases: microcephaly/primordial dwarfisms, and ciliopathies, respectively.