Abnormal mitosis in p53-/- Clara cells

Chris Armit, Department of Pathology, University of Edinburgh

Clara cells are a population of progenitor cells which reside predominantly in the bronchioles, but which migrate to sites of injury in damaged lung where they assist in airway remodelling. Clara cells proliferate and differentiate to replenish the pool of ciliated cells at sites of damaged and denuded epithelium, but may additionally adopt a tumourigenic phenotype by acquiring mutations in key cell cycle regulatory genes.

The p53 oncosupressor protein is a critical mediator of the response to injury in mammalian cells. p53 is mutationally inactivated in the majority of human lung malignancies, a phenomenon which highlights its importance in proper growth control. However, effects of p53 distinct from growth control are observed in Clara cells. Clara cells isolated and cultured from gene-targeted mice germline deficient in p53 display cell division abnormalities whereby nuclei fail to segregate mitotically during the final stage of the cell cycle. Spontaneous binucleation and the formation of multiple spindle poles in these cultures highlight functions of wild type p53 protein in the formation of bipolar spindles.