A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila

G3: Genes, Genomes, Genetics

Barry Ganetzky^1¹  Grace Boekhoff-Falk^2²  Carin Loewen^1³ 

[1] Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487^3;Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705^2;Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706^1

关键词: Drosophila;    brain tumor;    neurodegeneration;    cell proliferation;    prolyl4-hydroxylase;   

DOI  :  10.1534/g3.118.200627

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor ( brat ) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, brat^cheesehead ( brat^chs ), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult brat^chs mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.

【 授权许可】

CC BY