טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentYevgenia Lugassy
SubjectDevelopment and Tumorigenesis: Malignant Brain Tumor, a
Drosophila Tumor Suppressor Gene, is Involved in
Terminal Differentiation by
Transcription Repression...
DepartmentDepartment of Biology
Supervisor Assistant Professor Lev Ze'ev


Abstract

Mutations in five Drosophila tumor suppressor genes give rise to larval brain tumors. Three of these brain tumor suppressors, scribble, lgl, and dlg, are engaged in asymmetric division required for cell-fate determination of the embryonic neuroblasts. Unlike these genes, the other two, brat and mbt, are not involved in this process. In this study we showed that Mbt can also block cell proliferation in a variety of tissues and organs. Brat functioned similarly to Mbt but Lgl has no anti-proliferative effect whatsoever. Apparently the early group, including scrib, dlg, and lgl, is involved in cell fate determination of neuroblast daughter cells into ganglion mother cells (GMCs), and the late group, including brat and mbt, is associated with terminal differentiation of GMCs into mature neurons, requiring cell division arrest. Since Mbt has structural homology with Polycomb group proteins (PcG) associated with gene repression at the chromatin level, we studied genetic interactions between Mbt and Polycomb (Pc), a PcG protein. Temperature-sensitive mutation of mbt abrogates the normal function of Pc, resulting in homeotic transformations of the leg identity in male flies. Thus, Mbt can be identified as PcG protein due to its structural homology to other PcG proteins, and its genetic interaction with Pc. It is reasonable to assume that mbt and brat drive terminal differentiation by blocking cell divisions of GMCs, probably by utilizing the PcG repression machinery. Consequently, mutations in prevent blockage of GMCs divisions, resulting in cellular transformation.