In insects, functions of the vertebrate kidneys are carried out by Malpighian tubules (MT) and nephrocytes [see 'kidney disease (fly models overview)' FBhh0000738]. In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, if both daughter cells behave like stem cells, formation of hyperplastic tumors is observed. In a screen for mutations that affect MT stem cell self-renewal and differentiation, it was determined that loss of the polarity gene scribble (scrib) or of the Hippo signaling gene salvador (sav) increased proliferation. Stem cells expressing activated Ras (Ras85DV12) also exhibit increased proliferation, as well as reduced cell death and failure to differentiate; metastatic phenotypes are not observed.
In this system, the simultaneous loss of scrib does not further enhance the Ras85DV12 mutant phenotype. This is in contrast to systems modeling epithelial cancer initiation and progression in flies, in which expression of scrib loss-of-function alleles in combination with the Ras85DV12 activated mutation results in extensive tumors and metastatic phenotypes (see FBhh0000585).
[updated Oct. 2019 by FlyBase; FBrf0222196]