טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentKnaneh Hanaa
SubjectCharacterization of the Role of dMyc-Groucho Shared Novel
Target Genes in Drosophila Development
DepartmentDepartment of Medicine
Supervisor Professor Amir )Oryan )Orian
Full Thesis textFull thesis text - English Version


Abstract

The function and regulation of dmyc is crucial for Drosophila embryonic development. dMyc is a Drosophila member of the Myc family of bHLHZip transcription factors network  and is involved in cell growth, proliferation, apoptosis and differentiation. Deregulated expression of mammalian Myc proteins leads to malignant transformation, genetic instability and apoptosis. Furthermore, the myc family of oncogenes is intimately involved in the genesis of cancer including neuroectodermal tumors such as neuroblastomas.

The Myc protein functions within the context of a transcriptional network where it dimerizes with the small bHLHZ protein Max. Myc-Max heterodimers specifically bind to the E-box sequence CACGTG, and recruit chromatin modifying complexes that positively regulate genes expression. Max also dimerizes with the Myc antagonist Mxd proteins Mxd(Mad/dMnt) to give rise to Max-Mxd heterodimers. In contrast to Myc-Max heterodimers, these heterodimers are associated with gene repression.

Using Drosophila as a model system and the DamID method, 288 direct targets of the Myc protein were identified. Out of 288 Myc direct targets, 117 genes were bound only by Myc but not by either Mnt or Max. In addition, a comparison between the direct targets of the dMyc network and the direct targets of the Hairy repressor and its associated co-repressors unexpectedly revealed a significant overlap between dMyc and Groucho targets revealing 37 shared transcriptional direct targets. Out of the 37 shared dMyc-Gro targets, 11 are still of unknown function [2]. In this work, I further classified these 11 novel targets and focused on targets exhibiting specific expression patterns in the developing neuroectoderm and gonads. 

Specifically, my study was dedicated to the characterization of CG9705 as a novel dMyc-Gro target in the context of Egfr/myc and Notch/gro pathways. Through myc and gro gain of function and loss of function studies, in vitro and in vivo, the regulation of CG9705 was partially characterized. Our results combined with data mining indicate that CG9705 is a potential candidate involved in the regulation of  cell cycle, to have a role in early development and most likely to function as a translational repressor. It is most likely to be involved in regulating histone expression and hence to function in cell differentiation and mitosis.  Taken together, CG9705 may have a crucial function in neurogenesis and gonadogenesis as a realizator gene of the Egfr/myc pathway during early development.