Asymmetric division is a critical step in the differentiation of post-embryonic stem cells during which each stem cell generates one self-renewing and one differentiating daughter cell. Mutations in Drosophila genes that disrupt the process of asymmetric division have been studied as models of neural-stem-cell derived cancers. Genes studied include numb, mira, pros, pins, brat, and l(3)mbt.
Loss-of-function mutations that affect normal neuroblast differentiation in Drosophila often result in conspicuous phenotypes of overproliferation and tumorous expansion of the brain at the larval stage. In brat or pros mutants, both daughter cells of the normally asymmetric division grow and behave like neuroblasts, leading to the formation of larval brain tumors comprised primarily of neuroblast-like cells. A sensitive test of neoplastic transformation is transplantation of potential tumorous cells into the abdomen of adult hosts; cells are observed for proliferation and invasive behaviors. One of the earliest genes characterized in this transplantation assay was brat. Homozygous loss-of-function mutations of numb, mira, pros, and pins have also been tested in this assay; larval brain tissue carrying neuroblasts with any of these mutations grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. The tumors became immortal and could be re-transplanted into new hosts for years.
See also reports for well-studied disease models using specific genes, 'cancer, neural stem cell, TRIM2,3-related' (FBhh0000772, using the fly gene brat) and 'cancer, neural stem cell, L3MBTL-related' (FBhh0000773, using the fly gene l(3)mbt).
[updated Jan. 2019 by FlyBase; FBrf0222196]