Centrosomes establish a mitotic spindle geometry that facilitates correct kinetochore–microtubule attachments, contributing to the fidelity of chromosome segregation.

The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development.

Gene targeting was used to ablate Cep135, a component of the centriolar cartwheel, in chicken DT40 cells. Cep135-deficient cells showed no major defects in centrosome composition or function, although centrosome amplification after HU treatment increased significantly. EM revealed an unusual structure in the lumen of Cep135-null centrioles.