טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentKlein Yifat
SubjectKey Factors in the Sensory Organ development in the
Embryonic PNS of the Fruit Fly
DepartmentDepartment of Medicine
Supervisor Professor Adi Salzberg
Full Thesis textFull thesis text - English Version


Abstract

The chordotonal organs (CHOs) serve as the major proprioceptors in Drosophila.  Each CHO contains a bipolar neuron, a glial cell, two accessory cells, called the cap and ligament, and two epidermal attachment cells termed cap attachment (CA) and ligament attachment (LA) cells. The LA cell is not derived from the CHO lineage and is recruited by the ligament cells through an EFGR-dependent mechanism. The lateral CHOs (lch5) are born in the dorsal region of the embryo and migrate ventrally to assume their lateral position.

Stripe (Sr) is a triple zinc finger transcription factor of the Egr family. The sr gene encodes two splice-forms termed SrA and SrB, which probably play distinct roles in lch5 development. SrB is expressed in the LA, CA and ligament cells of the lch5 organ, whereas SrA is expressed only in the attachment cells, following SrB expression. Here we show that autonomous activity of Sr is both required and sufficient for LA cell differentiation. In certain domains in the ectoderm, Sr can turn epidermal cells into LA cells upon ectopic expression. Both splice-forms are able to induce, upon ectopic expression, proteins that are required for CHO attachment cell maturation. In the ligament cells SrB is essential for terminal differentiation, for proper migration and for glial cell-like functions which affect neural survival. In the absence of Sr activity, the CA cells fail to express β1-tubulin (β1-tub), and the ligament cells fail to express normal levels of cytoskeletal factors such as β1-tub, Shortstop, βPS-integrin and the CHO-specific isoform of α-tubulin. Ectopic expression of Sr diverts the ligament cells from their normal route of migration. Autonomous expression of Sr within the lch5 cells fully rescues the migrational defects associated with sr loss-of-function, suggesting that Sr acts autonomously in the migrating cells. The expression of β1-tub in the lch5 attachment cells is regulated by another transcription factor, called Delilah (Dei). Dei is a bHLH protein which is expressed in lch5 accessory and attachment cells. Dei is required for the terminal differentiation of the attachment cells. The absence of Dei activity is largely manifested in the loss of β1-tub in these cells. In summary this work demonstrates that Sr is required within the ligament cells for responding to positional cues that guide lch5 migration. SrB is required for LA cell differentiation, whereas both SrB SrA and Dei are required for attachment cell maturation.