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Mechanical control of tissue growth through Hippo signaling

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TitleInfo
Title
Mechanical control of tissue growth through Hippo signaling
Name (type = personal)
NamePart (type = family)
Pan
NamePart (type = given)
Yuanwang
NamePart (type = date)
1988-
DisplayForm
Yuanwang Pan
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Irvine
NamePart (type = given)
Kenneth
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Kenneth Irvine
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Advisory Committee
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RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Soto
NamePart (type = given)
Martha
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Martha Soto
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Advisory Committee
Role
RoleTerm (authority = RULIB)
co-chair
Name (type = personal)
NamePart (type = family)
Padgett
NamePart (type = given)
Richard
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Richard Padgett
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kramer
NamePart (type = given)
Sunita
DisplayForm
Sunita Kramer
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
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Tissue growth needs to be properly controlled for organs to reach their correct size and shape, but the mechanisms that control growth during normal development are not fully understood. Recently, mechanical forces have emerged as an important regulator of tissue growth: high cytoskeletal tension enhances tissue growth while low cytoskeletal tension decreases tissue growth. Our lab also discovered that cytoskeletal tension regulates tissue growth through a biomechanical Hippo signaling pathway. However, how mechanical forces are modulated and experienced by cells within developing tissues is not clear. Moreover, whether and how mechanical forces contribute to growth patterns in vivo was not know. To answer these questions, I focused my study on the mechanical feedback model of tissue growth and how mechanical forces contribute to growth control in vivo. Mechanical feedback. How cells sense mechanical forces and coordinate their growth rates is not clear. One way cells could experience tension in a growing organ was provided by the mechanical feedback model: 1) differential growth rates could lead to local tissue compression as faster-growing cells push against surrounding slower-growing cells, and 2) that this local tissue compression would then decrease growth, thereby restoring even growth rates and minimizing further compression. I tested the mechanical feedback hypothesis by inducing differential growth in Drosophila wing disc epithelia through distinct approaches. I showed that differential growth triggers a mechanical response that lowers cytoskeletal tension along apical cell junctions within faster-growing cells. This reduced tension modulates a biomechanical Hippo pathway, decreasing recruitment of Ajuba LIM protein and the Hippo pathway kinase Warts to junctions, and reducing the activity of the growth-promoting transcription factor Yorkie. This provides the experimental support and a molecular mechanism for lowering growth rates within faster-growing cells by mechanical feedback. Collaborating with another lab, we also proposed a theoretical model to explain the observed reduction of tension within faster-growing clones, supported through simulations using a modified vertex model. Finally, I found that bypassing mechanical feedback induces tissue distortions and inhomogeneous growth. Thus my research further identifies the roles of mechanical feedback in maintaining tissue shape and controlling patterned growth rates during development. Growth control in vivo. How tissue growth is modulated in vivo is an important but unsolved question in developmental biology. During Drosophila wing disc development, the cell proliferation rate gradually slows down. But what contributes to this growth reduction is not clear. Recent studies identified that mechanical stress and Hippo signaling are required in organ size control. However, how they are regulated in vivo and their contributions to normal development are largely unknown. I discovered that the activity of the Hippo signaling transcriptional activator Yorkie gradually decreases in the central region of the developing Drosophila wing disc. Spatial and temporal changes in Yorkie activity can be explained by changes in cytoskeletal tension and biomechanical regulators of Hippo signaling. These changes in cellular biomechanics correlate with changes in cell density, and experimental manipulations of cell density are sufficient to alter biomechanical Hippo signaling and Yorkie activity. I also related the pattern of Yorkie activity in older discs to patterns of cell proliferation. This study shows that spatial differences in Hippo signaling contribute to spatial patterns of growth in vivo, and provides evidence for a contribution of tissue mechanics to regulating patterns of Yorkie activity and growth during wing development.
Subject (authority = RUETD)
Topic
Cell and Developmental Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8709
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 149 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Tissues--Growth
Note (type = statement of responsibility)
by Yuanwang Pan
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3MS3X6M
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
Yuanwang
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-03-18 12:39:45
AssociatedEntity
Name
Yuanwang Pan
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
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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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2019-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2018-03-18T16:15:48
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2018-03-18T16:15:48
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