Mutations in the Ras genes and signaling pathways are not only common in human cancers, but also cause several developmental disorders including Costello syndrome. Here, Cristina Santoriello and colleagues use zebrafish to study mutant oncogenic H-RAS during development and find that fish carrying the germline H-RAS mutation have several hallmarks of Costello syndrome. These include cranio-facial abnormalities and tumorigenesis, as is seen in the human disease. Furthermore, mutant fish exhibit cellular senescence in adult progenitor cells. Their work presents a new animal model for studying tumor development and Costello syndrome, and encourages further examination of cellular senescence underlying the age-related symptoms of Costello patients.

Page 56

2009