טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentMatia Nirit
SubjectThe Roles of the delilah Gene in Wing
Development in Drosophila
DepartmentDepartment of Medicine
Supervisor Professor Adi Salzberg
Full Thesis textFull thesis text - English Version


Abstract

Delilah (Dei) is a bHLH protein whose expression in the embryo is restricted mainly to tendon cells, which attach muscles to the epidermis, and to accessory cells of the chordotonal organs (ChO) that serve as propriceptors in Drosophila. The expression of Dei exclusively in cells that serve as attachment sites to neighboring cells, suggests that it plays a role in regulating adhesion processes between different cell types. A powerful model system for studying adhesion processes in Drosophila is the wing. The wing is composed of two cell types, veins and interveins, which acquire very different adhesive qualities during their differentiation. The intervein cells adhere tightly to each other, whereas the vein cells do not. We used the fly wing as a model system to investigate the role of Dei in regulating the differentiation of cells with different adhesive properties.

In this work we show that in the developing wing Dei is expressed exclusively in intervein cells and is excluded from vein cells. Phenotypic analyses of wings of dei loss-of-function mutants suggest that Dei is required to promote intervein differentiation and prevent vein development. Ectopic expression of Dei in the developing veins disturbed normal vein differentiation and led to intervein-like differentiation.

Studying the regulation of dei's expression revealed that it is regulated by the main pathway that divide the wing into vein and intervein territories. The vein-determining genes, Drosophila epidermal growth factor receptor and ventral veinless, negatively regulate dei's expression. Notch and blistered, which mediate intervein differentiation, positively regulate dei's expression. We also identified downstream targets of Dei. Dei is involved in the regulation of integrins which mediate the adhesion between different cell layers in all organisms, and are crucial for the attachment of the two wing layers in Drosophila. Loss of integrins results in wing blisters. Here we show that Dei positively regulates the expression of βPS integrin and may negatively regulate the expression of αPS2 integrin. It does not affect the expression of αPS1 integrin. These observations suggest that Dei plays an important role in developmental crossroads, where cells that originate from the same tissue acquire different adhesive properties. Dei is required in these situations to execute a certain developmental program that is determined by major signaling pathways, such as DER and Notch. Where active, Dei regulates the expression of cell adhesion molecules, such as integrins, that are required for the "sticky" cells to adopt their final fate.