Fragile X Protein Regulates Cellular Proliferation and Oocyte Polarity by Controlling cb1 Levels During Drosophila Oogenesis

Persistent Link:
http://hdl.handle.net/10150/193434
Title:
Fragile X Protein Regulates Cellular Proliferation and Oocyte Polarity by Controlling cb1 Levels During Drosophila Oogenesis
Author:
Epstein, Andrew Michael
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Fragile X Protein (FMRP) is an RNA binding protein linked to the most common form of inherited mental retardation, Fragile X syndrome (FraX). Despite its ubiquitous expression and presence of non-neuronal phenotypes, FMRP function remains understudied outside of neural and synaptic development. In addition to severe cognitive deficits, FraX etiology also includes postpubescent macroorchidism, which is thought to occur due to overproliferation of the germline. Using a Drosophila model for FraX, I have shown that FMRP controls germline proliferation as well as dorso-ventral polarity during oogenesis. dFmr1 null ovaries exhibit egg chambers with increased numbers of germ cells and ventralized embryos. The number of cyclin E and phosphohistone H3 positive cells is increased in dFmr1 germaria compared to wild-type, suggesting that the mutant germline cells exhibit defects in proliferation. In addition, BrdU incorporation is increased during vitellogenesis, consistent with a prolonged S phase for endoreplicating nurse cells. Here I report the FMRP controls the levels of cbl mRNA in the ovary and that the overproliferation and polarity defects found in dFmr1 ovaries can be rescued by reducing cbl dosage in half. These data suggest a model whereby FMRP regulates cellular proliferation and polarity during oogenesis by controlling the E3 ubiquitin ligase cbl.
Type:
text; Electronic Thesis
Keywords:
cbl; Drosophila; Fragile X; oocyte polarity; Oogenesis
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Molecular & Cellular Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Zarnescu, Daniela C.
Committee Chair:
Zarnescu, Daniela C.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleFragile X Protein Regulates Cellular Proliferation and Oocyte Polarity by Controlling cb1 Levels During Drosophila Oogenesisen_US
dc.creatorEpstein, Andrew Michaelen_US
dc.contributor.authorEpstein, Andrew Michaelen_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractFragile X Protein (FMRP) is an RNA binding protein linked to the most common form of inherited mental retardation, Fragile X syndrome (FraX). Despite its ubiquitous expression and presence of non-neuronal phenotypes, FMRP function remains understudied outside of neural and synaptic development. In addition to severe cognitive deficits, FraX etiology also includes postpubescent macroorchidism, which is thought to occur due to overproliferation of the germline. Using a Drosophila model for FraX, I have shown that FMRP controls germline proliferation as well as dorso-ventral polarity during oogenesis. dFmr1 null ovaries exhibit egg chambers with increased numbers of germ cells and ventralized embryos. The number of cyclin E and phosphohistone H3 positive cells is increased in dFmr1 germaria compared to wild-type, suggesting that the mutant germline cells exhibit defects in proliferation. In addition, BrdU incorporation is increased during vitellogenesis, consistent with a prolonged S phase for endoreplicating nurse cells. Here I report the FMRP controls the levels of cbl mRNA in the ovary and that the overproliferation and polarity defects found in dFmr1 ovaries can be rescued by reducing cbl dosage in half. These data suggest a model whereby FMRP regulates cellular proliferation and polarity during oogenesis by controlling the E3 ubiquitin ligase cbl.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
dc.subjectcblen_US
dc.subjectDrosophilaen_US
dc.subjectFragile Xen_US
dc.subjectoocyte polarityen_US
dc.subjectOogenesisen_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineMolecular & Cellular Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorZarnescu, Daniela C.en_US
dc.contributor.chairZarnescu, Daniela C.en_US
dc.contributor.committeememberBosco, Giovannien_US
dc.contributor.committeememberTax, Frans E.en_US
dc.identifier.proquest10008en_US
dc.identifier.oclc659750585en_US
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