The Large Maf Transcription Factor Traffic Jam Regulates Collective Cell Migration During Drosophila Oogenesis
Year: 2015
Type: dissertation
Abstract: Collective cell migration is a fundamental process throughout development. The migrating border cell cluster (BCC) in the Drosophila ovary is a good in-vivo model system to study this process. My work focuses on the function of the large Maf transcription factor, Traffic Jam (Tj), in regulating BCC migration. Tj has a dual function in both promoting and inhibiting BCC migration, as reduction or increase of tj expression leads to migration delays. I found a genetic interaction between Tj and three factors known to promote BCC migration: an inhibitor of the JAK/Stat pathway, Socs36E, the transcription factor Slow border cells (Slbo), and the adhesion molecule DEcadherin (DEcad). At high expression level, Tj enhances the expression of Socs36E, which subsequently inhibits JAK/Stat and causes reduction of Slbo. High Tj expression also inhibits DEcad upregulation in the BCC. Activation of Slbo, which is induced by JAK/Stat, leads to a natural downregulation of Tj. This low expression level of Tj maintains Slbo expression in the BCC, which allows for DEcad upregulation. My work has shown that Tj is an important component of this regulatory network, which allows for proper BCC migration. Analysis of BCC morphology reveals that Tj also functions in regulating the formation of actin-based cellular protrusions. These protrusions are normally extended by border cells and are necessary for its movement. Altering Tj expression leads to abnormal organization of the actin cytoskeleton and morphology of the protrusions. This effect does not appear to be mediated through Slbo or DEcad, which are known to regulate actin. A genome-wide microarray screen identified serine/threonine kinase Protein Kinase C δ (PKCδ) as a putative target of Tj. Changing PKCδ expression in the BCC also causes abnormal organization of actin filaments. Genetic interaction studies suggest that Tj regulates actin organization through upregulating PKCδ. Furthermore, altering Tj or PKCδ expression changes the distribution pattern of an actin filament elongation factor, Enabled, in the BCC. My results have identified Tj and its putative downstream effector, PKCδ, as crucial regulators of the actin cytoskeleton and cellular protrusions in the BCC.
Source: TSpace (University of Toronto)
Author: Felix Gunawan
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2929696733