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(3)mbt. In human, there are three genes orthologous to Dmel\l(3)mbt, L3MBTL3, L3MBTL4, and L3MBTL1, which encode chromatin-interacting transcriptional repressors. Loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\l(3)mbt.
None of the three human genes, L3MBTL3, L3MBTL4 or L3MBTL1, has been introduced into flies.
At restrictive temperatures, a temperature-sensitive allele of Dmel\l(3)mbt is lethal in the early pupal stage; the length of the larval stage is greatly extended. The brain hemispheres are up to five times larger in older homozygous larvae raised at the restrictive temperature compared to mature wild-type larvae. Using a tissue transplant assay for neoplastic capacity, homozygous larval brain tissue transplanted into the abdomens of wild-type adult hosts develops into extensive tumors, taking over the entire abdomen of the host in many cases. Physical and genetic interactions have been described for Dmel\l(3)mbt; see below and in the l(3)mbt 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.
L3MBTL3, L3MBTL4 and L3MBTL1 encode members of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. [Gene Cards, L3MBTL3; 2018.03.22]
Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.
Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.
Many to one: 3 human to 1 Drosophila; the human genes are L3MBTL3, L3MBTL4, and L3MBTL1.
Moderate-scoring ortholog of human L3MBTL3, L3MBTL4, and L3MBTL1 (1 Drosophila to 3 human). Dmel\l(3)mbt shares 28-31% identity and 42-46% similarity with the human genes.
