Date of Award

Spring 1-1-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Mark Winey

Second Advisor

Greg Odorizzi

Third Advisor

Tin Tin Su

Fourth Advisor

Todd Blankenship

Fifth Advisor

Kevin Jones

Abstract

Centralspindlin is an essential protein complex in all metazoans well-studied for its essential role in cytokinesis. Emerging evidence suggests centralspindlin has important interphase functions as well. Through its regulation of Rho family small GTPases at the plasma membrane, the centralspindlin complex is able to effect a number of cellular process including cell adhesion and cell migration. In this thesis I explored centralspindlin's function in development and tissue morphogenesis. In addition I investigated potential nuclear functions of the centralspindlin complex. To address these potential functions of centralspindlin I used the model organism Drosophila melanogaster.

I found centralspindlin is essential for migration of Drosophila wing disc cells and proper thorax closure in addition to its role in cytokinesis. The subcellular localization of centralspindlin is important for its function in thorax development as perturbation of centralspindlin's cytoplasmic activity results in thorax defects. I also found centralspindlin was required for the formation of sensory organ bristles. I found no effect of centralspindlin depletion or mutation on signaling pathways involved in sensory organ differentiation indicating this is likely a secondary result of thorax closure and cell cycle defects. I used Drosophila salivary glands to investigate nuclear functions of centralspindlin but was unable to discern a clear function. Centralspindlin localizes to the nuclei and chromosomes of these cells but does not seem to be involved in either transcription or DNA replication.

My investigations have demonstrated centralspindlin is a multi-functional protein complex responsible for regulating various cellular events including cytokinesis, cell migration, and cell adhesion.

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