• brain cancer

The role of neuroblasts in the development of the Drosophila larval/adult brain has served as a model for the role of adult neural stem cells in normal neural development and in tumor formation. 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. Based on this phenotype, a number of genes impacting this process in flies have been identified. This report describes a human disease model using the fly gene l(2)gl. In human, there are two genes orthologous to Dmel\l(2)gl, the cortical cytoskeletal proteins LLGL1 and LLGL2. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\l(2)gl.

A tagged wild-type transgene of human Hsap\LLGL1 has been introduced into flies; partial heterologous rescue (functional complementation) of the homozygous Dmel\l(2)gl lethal phenotype is observed.

Animals homozygous for loss-of-function mutations of Dmel\l(2)gl typically die during the larval stage and exhibit abnormal overproliferation of tissues, including in the brain, imaginal discs, and hematopoietic organs; cell-polarity defects are observed. Using a tissue transplant assay for neoplastic capacity, discs of larvae transplanted into wild-type adult female abdomens form large contained tumors; transplanted optic primordia from larval brains form invasive neuroblastomas, which grow rapidly, killing the host within 7-14 days; they can be serially cultured in adult abdomens. Multiple physical and many genetic interactions for Dmel\l(2)gl have been described; see below and in the gene report for l(2)gl.

See related human disease model reports: human disease models for epithelial cancers related to the LLGL gene (FBhh0000591, FBhh0000590, FBhh0000588) and human disease models for malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403, FBhh0000404, FBhh0000668).

[updated Mar. 2018 by FlyBase; FBrf0222196]