טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentElla Efraim
SubjectTumor Suppressor Genes in the Fruit Fly Drosophila
Melanogaster: Interaction with the Repressing
System of the Polycomb Group Proteins
DepartmentDepartment of Biology
Supervisor Assistant Professor Lev Ze'ev
Full Thesis text - in Hebrew Full thesis text - Hebrew Version


Abstract

Tumor-like neoplasm can be formed in Drosophila melanogaster larval brains by inactivating both alleles of several genes acting like tumor suppressor genes. Some of these genes were implicated in regulating neuroblast stem cells polarity, enabling asymmetric division into a neuroblast and a ganglion mother cell (GMC). However two brain tumor suppressors - lethal(3)malignant brain tumor (l(3)mbt) and brain tumor (brat) - are not involved in this process, but probably associated with terminal differentiation of the GMC daughter  cell.
 The Polycomb Group (PcG) of proteins is involved in the maintenance of repression of Hox and other developmental control genes. The Mbt protein has significant structural homology with members of the PcG proteins. In addition, Mbt and Polycomb (Pc) share similar binding sites on polytene chromosomes (Hobte-Michael and Gateff, unpublished results). The aim of this study was to explore possible genetic interaction between l(3)mbt and the Polycomb repression system. brat was also included in the study.
We used a plethora of mutated alleles of l(3)mbt and brat to detect changes in a Pc phenotype, extra sex combs on the second and third legs. We were able to establish a clear agonistic relationship between l(3)mbt and Pc, suggesting that  l(3)mbt is involved in directing or enhancing the repressive function of the Pc complexes. The Brat protein is a translational repressor, and has no structural similarity with any of the PcG proteins. Interestingly, mutated brat alleles also interacted with Pc and with posterior sex combs (psc), another member of the Pc core complexes. However, in this case the interaction was antagonistic, reducing the number of extra sex combs. The reason for this apparent difference is yet unknown. Our results suggest that the interaction of the two brain tumor suppressors l(3)mbt and brat with the Polycomb system might also be important for their putative role during the terminal differentiation of GMCs.