dc.creator | Sitaram, Poojitha | |
dc.date.accessioned | 2020-08-22T21:17:21Z | |
dc.date.available | 2015-11-08 | |
dc.date.issued | 2013-11-08 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-10292013-141930 | |
dc.identifier.uri | http://hdl.handle.net/1803/14386 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | dynein | |
dc.subject | nucleus | |
dc.subject | centrosomes | |
dc.subject | meiosis | |
dc.subject | <i>Drosophila</i> | |
dc.subject | spermatogenesis | |
dc.subject | oogenesis | |
dc.subject | Lis-1 | |
dc.subject | asunder | |
dc.title | Regulation of Dynein-Dynactin during <i>Drosophila</i> Gametogenesis | |
dc.type | dissertation | |
dc.contributor.committeeMember | David M. Bader | |
dc.contributor.committeeMember | Matthew J. Tyska | |
dc.contributor.committeeMember | Katherine L. Friedman | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-11-08 | |
local.embargo.lift | 2015-11-08 | |
dc.contributor.committeeChair | David M.Miller III | |
dc.contributor.committeeChair | Laura A. Lee | |