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. Asymmetric cell division, a critical part of the process of stem cell renewal vs. differentiation, has been extensively studied in the context of this system. 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 brat, a negative regulator of translation. In human, there are two genes orthologous to Dmel\brat, TRIM3 and TRIM2, members of the tripartite motif (TRIM) family. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\brat.
Neither human gene, TRIM3 or TRIM2, has been introduced into flies. In humans, there is evidence implicating TRIM3 in malignant glioma (Boulay, et al, 2009; pubmed:19250537).
Animals homozygous for amorphic mutations of Dmel\brat typically die during the larval stage and exhibit abnormal overproliferation in the brain; there is a dramatic increase in neuroblast number. Using a tissue transplant assay for neoplastic capacity, hemizygous larval brain tissue transplanted into the abdomens of wild-type adult female hosts shows unrestrained and invasive growth. Additional phenotypes have been described using somatic clones or less severe mutations. Many physical and genetic interactions have been described for Dmel\brat; see below and in the brat gene report.
See also related human disease model reports for malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403, FBhh0000404, FBhh0000668).
[updated Mar. 2018 by FlyBase; FBrf0222196]
Neural stem cells have the ability to self-renew and give rise to neurons and glial cells. In Drosophila, the role and regulation of neural stem cells (neuroblasts) at multiple stages has been studied extensively. The study of neuroblasts in the development of the larval/adult brain has served as a model for the role of adult stem cells in normal neural development and in tumor formation. Asymmetric cell division, a critical part of the process of stem cell renewal vs. differentiation, has been studied in the context of this system.
The proteins encoded by TRIM3 and TRIM2 are members of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RING finger proteins. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The TRIM3 and TRIM2 proteins localize to cytoplasmic filaments. [Gene Cards, TRIM3, TRIM2; 2018.03.22]
The Drosophila ortholog, brat, has been shown to negatively regulate translation. (FlyBase, brat gene report; 2018.03.22]
Many to many: 2 human to 2 Drosophila.
Many to many: 2 human to 2 Drosophila.
Low-scoring ortholog of human TRIM3 and TRIM2 (2 Drosophila to 2 human). Dmel\brat shares 23-25% identity and 39-41% similarity with the human genes.
