טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentReem Eran
SubjectBrain Neoplasm in Drosophila: Genetic and Functional
Interaction between the Two Tumor Suppressor Genes
mbt and brat
DepartmentDepartment of Biology
Supervisor Assistant Professor Ze'ev Lev


Abstract

Recessive mutations in the Drosophila tumor suppressor gene lethal(3)malignant brain tumor (mbt) lead to malignant neoplasm in the adult optic centers and death at the 3rd larval stage. The Mbt protein has four known protein motifs: 1) a lysine rich area; 2) Two zinc fingers, which act as a DNA or protein binding domain; 3) A SPM motif; and 4) three "Mbt repeat". The SPM and the Mbt motifs are important for the proper function of proteins from the Polycomb Group.

          We used ectopic expression of the Mbt protein in several tissues and developmental stages. Our results indicate that mbt can block cell proliferation and differentiation, but probably does not induce apoptosis. Ectopic expression of positive cell cycle regulators such as Cyclin E and the transcription factor Eyeless resulted in partial rescue of the Mbt phenotype, suggesting that Mbt blocks proliferation by arresting the cell-cycle.

Evaluation of the ectopic expression phenotype of three out of the four brain tumor suppressor genes: lgl, brat, and mbt , show a remarkable similarity between the mbt and brat phenotypes that differ from the lgl phenotype. This result may indicate a different function for Mbt and Brat rather than Lgl. Indeed, genetic assays prove the existence of interactions between the two genes, which involve homeotic regulation.

In summary, our results indicate that mbt may play a double role: blocking proliferation and regulating differentiation. This double role of mbt during neuroblast proliferation and differentiation in the embryo may be the reason for its role as a tumor suppressor gene.