טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentInbal Adi
SubjectDevelopmental and Functional Studies of HTH and VVL, Two
Transcription Factors involved in PNS Development
in Drosophila
DepartmentDepartment of Medicine
Supervisor Professor Adi Salzberg


Abstract

Homothorax (HTH) is a homeobox-containing protein, which binds to the homeotic cofactor Extradenticle (EXD) and translocates it to the nucleus.  HTH can bind DNA as a part of ternary HTH/EXD/HOX complexes, but little is known about the transcription regulating function of HTH-containing complexes in vivo. We present genetic evidence, from in vivo studies, for the transcriptional-activating function of HTH. We used a chimeric protein comprising HTH fused to the Engrailed (EN) repression domain in order to force HTH to function as a transcriptional-repressor and a chimeric protein comprising HTH fused to the VP16 activation domain, thereby forcing HTH to function as a transcriptional-activator. Expression of the repressing form of HTH in otherwise wild type imaginal discs phenocopied hth loss-of-function, whereas the activating form caused typical hth gain-of-function phenotypes. Thus, the repressing form was working as an antimorph, suggesting that normally HTH is required to activate the transcription of downstream target genes. We also show that HTH functions as a transcriptional-activator during embryonic PNS development.

In the PNS of embryos homozygous for mild hth loss-of-function alleles, the 5 lateral chordotonal (lch5) neurons fail to migrate to their correct position. Mutations in the u-turn (ut) locus have been shown to result in a highly similar PNS phenotype, suggesting that ut and hth may function in the same developmental pathway. We show that ut is allelic to ventral veinless (vvl). We find that in the absence of VVL cell fates within lch5 organs are determined properly, and the entire organ is misplaced. Based on our observations we propose a two-step model for lch5 localization. VVL seems to function both autonomously and non-autonomously in this process. VVL is also required for normal development of embryonic and adult external sensory organs.