Dynein, a microtubule motor protein complex, plays critical roles in cell-cycle progression in many systems. The dynein accessory factor <i>LIS1</i>, 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 <i>Drosophila</i> homolog of human <i>LIS1</i>. We found defects in centrosome migration and attachments in <i>Lis-1</i> spermatocytes and spermatids. The localization pattern of LIS-1 protein throughout <i>Drosophila</i> spermatogenesis mirrors that of dynein, and dynein recruitment to the nuclear surface and spindle poles is severely reduced in <i>Lis-1</i> male germ cells. We previously identified <i>asunder</i> (<i>asun</i>) as a novel regulator of dynein localization during <i>Drosophila</i> spermatogenesis. We present a model in which <i>Lis-1</i> and <i>asun</i> cooperate to regulate dynein localization and centrosome positioning during <i>Drosophila</i> spermatogenesis.
Expression of <i>asun</i> is much higher in <i>Drosophila</i> 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 <i>asun</i> (<i>asun<sup>d93</sup></i>). <i>asun<sup>d93</sup></i> females lay very few eggs, and a majority of these eggs are ventralized, possibly as a result of mislocalization of <i>gurken</i> transcripts, a dynein-regulated step, within <i>asun<sup>d93</sup></i> oocytes. Dynein localization and dynein-mediated processes are disrupted in <i>asun<sup>d93</sup></i> oocytes. Taken together, our data indicate that <i>asun</i> is a critical regulator of dynein during <i>Drosophila</i> gametogenesis.
As <i>asun</i> plays a conserved role in regulating dynein during <i>Drosophila</i> gametogenesis, we sought to identify other proteins that cooperate with <i>asun</i> 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 <i>asun</i> 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 <i>asun</i> to regulate dynein during <i>Drosophila</i> spermatogenesis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-10292013-141930 |
| Date | 08 November 2013 |
| Creators | Sitaram, Poojitha |
| Contributors | David M. Bader, Matthew J. Tyska, Katherine L. Friedman, David M.Miller III, Laura A. Lee |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-10292013-141930/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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