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Molecular mechanism of FAT signaling pathway coordinating growth and patterning in drosphila melanogaster

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TitleInfo
Title
Molecular mechanism of FAT signaling pathway coordinating growth and patterning in drosphila melanogaster
Name (type = personal)
NamePart (type = family)
Pan
NamePart (type = given)
Guohui
NamePart (type = date)
1982-
DisplayForm
Guohui Pan
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Padgett
NamePart (type = given)
Richard
DisplayForm
Richard Padgett
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Irvine
NamePart (type = given)
Kenneth
DisplayForm
Kenneth Irvine
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Matise
NamePart (type = given)
Michael
DisplayForm
Michael Matise
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Steward
NamePart (type = given)
Ruth
DisplayForm
Ruth Steward
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2013
DateOther (qualifier = exact); (type = degree)
2013-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
From an RNAi lines screen, our lab found the Drosophila Zyxin family gene, Zyx102 (Zyx) as a negative regulator of Fat-Hippo signaling. Epistasis analysis put Zyx between Dachs and Warts (Wts) in the Fat-branch, and Zyx-RNAi suppresses the reduction of Wts level by fat RNAi. Zyx partially co-localizes with Dachs, and its localization was not altered by manipulating other Fat-branch component. Zyx protein binds to Dachs, and Dachs stimulates binding of Zyx to Wts, suggesting a molecular mechanism for how Fat signaling regulates Wts through Dachs. Our results identified a new component of Fat signaling, and investigated possible molecular mechanism for signal transduction from Fat to Wts. Among the vast amount of genes involved in organ morphogenesis, Fat gene stands out as it transduces both growth cue and planar cell polarity (PCP). But the molecular mechanism underlying is unknown. A structure-function approach is recruited to figure out the motifs in Fat that are required for signal transduction mechanism. By a fat genomic Bac Clone, which is expressed under endogenous condition, activities that could be missed by over-expression can be revealed. We find out the PCP activity is evolutionarily conserved from Drosophila to mammals. And the Hippo and PCP activity can be largely separated at the level of the Fat receptor. A specific motif was identified to mainly impair Fat-Hippo activity and reduce Fat phosphorylation. Manipulating the potential phosphorylation sites in this motif gives similar phenotypes, implicating phosphorylation as an essential factor in Fat-Hippo signal transduction. This motif overlaps with the previously identified Dco binding site, but retains normal binding affinity. Another conserved four amino acid motif is crucial for Fat-PCP, while the Fat-Hippo activity is almost normal. And this motif contributes differently to multiple PCP assays, suggesting there are different kinds of PCP in Drosophila. Different Fat activity leads to distinctive Dachs localization pattern, and directly manipulating Dachs localization could phenocopy loss of Fat activity. Thus Dachs localization influences both Hippo and PCP phenotypes. Our results identify a conserved mechanism of Fat signaling, establish functional significances for Fat ICD motif, phosphorylation sites, and Dachs membrane localization to downstream pathways.
Subject (authority = RUETD)
Topic
Neuroscience
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4686
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
x, 96 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Guohui Pan
Subject (authority = ETD-LCSH)
Topic
Drosophila melanogaster--Development
Subject (authority = ETD-LCSH)
Topic
RNA
Subject (authority = ETD-LCSH)
Topic
Developmental neurobiology
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000068931
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T38914FJ
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Pan
GivenName
Guohui
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2013-04-14 23:09:52
AssociatedEntity
Name
Guohui Pan
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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