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Title page for ETD etd-10292013-141930

Type of Document Dissertation
Author Sitaram, Poojitha
Author's Email Address poojitha.spencer@gmail.com
URN etd-10292013-141930
Title Regulation of Dynein-Dynactin during Drosophila Gametogenesis
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
David M.Miller III Committee Chair
Laura A. Lee Committee Chair
David M. Bader Committee Member
Katherine L. Friedman Committee Member
Matthew J. Tyska Committee Member
  • dynein
  • nucleus
  • centrosomes
  • meiosis
  • Drosophila
  • spermatogenesis
  • oogenesis
  • Lis-1
  • asunder
Date of Defense 2013-10-07
Availability unrestricted
Dynein, a microtubule motor protein complex, plays critical roles in cell-cycle progression in many systems. The dynein accessory factor LIS1, first identified as a causative factor of the human brain disorder Lissencephaly when lost in one copy, is essential for a majority of the cellular activities of dynein. To gain insight into the in vivo functions of LIS1, we characterized a male-sterile allele of the Drosophila homolog of human LIS1. We found defects in centrosome migration and attachments in Lis-1 spermatocytes and spermatids. The localization pattern of LIS-1 protein throughout Drosophila spermatogenesis mirrors that of dynein, and dynein recruitment to the nuclear surface and spindle poles is severely reduced in Lis-1 male germ cells. We previously identified asunder (asun) as a novel regulator of dynein localization during Drosophila spermatogenesis. We present a model in which Lis-1 and asun cooperate to regulate dynein localization and centrosome positioning during Drosophila spermatogenesis.

Expression of asun is much higher in Drosophila ovaries than in testes. We therefore sought to determine whether ASUN plays roles in oogenesis. We characterized the female germline phenotypes of flies homozygous for a null allele of asun (asund93). asund93 females lay very few eggs, and a majority of these eggs are ventralized, possibly as a result of mislocalization of gurken transcripts, a dynein-regulated step, within asund93 oocytes. Dynein localization and dynein-mediated processes are disrupted in asund93 oocytes. Taken together, our data indicate that asun is a critical regulator of dynein during Drosophila gametogenesis.

As asun plays a conserved role in regulating dynein during Drosophila gametogenesis, we sought to identify other proteins that cooperate with asun to perform this function. We utilized a set of publicly available 2nd chromosome deficiency lines to initiate a dominant modifier screen to identify genes that could enhance or suppress the asun male phenotype when lost in one copy. Further testing will be required to identify and characterize the individual genes within these deficiency intervals that cooperate with asun to regulate dynein during Drosophila spermatogenesis.

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