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Regulation of Foxn4 during retina development
Descriptive
TitleInfo
Title
Regulation of Foxn4 during retina development
Name
(type = personal)
NamePart
(type = family)
Islam
NamePart
(type = given)
Mohammed Monirul
NamePart
(type = date)
1977-
DisplayForm
Mohammed Islam
Role
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(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Cai
NamePart
(type = given)
Li
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Li Cai
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Gartenberg
NamePart
(type = given)
Marc
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Marc Gartenberg
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Runnels
NamePart
(type = given)
Loren
DisplayForm
Loren Runnels
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Xiang
NamePart
(type = given)
Mengqing
DisplayForm
Mengqing Xiang
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)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-05
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Transcription factor forkhead box N4(Foxn4) is a key regulator involved in a variety of biologic processes in development and metabolism. In particular, Foxn4 plays an essential role in the genesis of amacrine and horizontal neurons from neural progenitors in the retina. Although the functions of Foxn4 have been well established, the transcriptional regulation of Foxn4 expression during progenitor cell differentiation remains unclear. The goal of this dissertation is to identify regulatory mechanisms that define the expression of Foxn4 during retinogenesis. Four evolutionarily conserved regions (CR1-CR4) from non-coding sequences of Foxn4 gene were computationally predicted as cis-elements. Their gene regulatory potential was individually tested in developing chick and mouse embryonic retina using electroporation transfection technique with a reporter assay system. In this dissertation, I describe that CR4.2 (a 129 bp DNA fragment of CR4, located approximately 50kb upstream of Foxn4 transcription start site) functions as a novel cis-regulator that directs retinal cell type specific gene expression. CR4.2 is preferentially active in the Foxn4 expressing cells, primarily in the differentiating and differentiated horizontal and amacrine cells as shown by reporter assays. Specific trans-acting factors, e.g., Meis1, were found to interact with CR4.2 by electrophoretic mobility shift assays (EMSA). Mutation and/or deletion of the Meis1 binding motif through site-directed mutagenesis diminishes the ability of CR4.2 to drive reporter GFP expression. Furthermore, the role of Meis1 in regulating Foxn4 expression during progenitor cell differentiation was determined using a RNAi-based gene silencing assay. Knockdown of Meis1 by short hairpin RNA (shRNA) specific to Meis1 genes abolishes gene regulatory activity of CR4.2, and further diminishes the endogenous level of Foxn4 expression. In addition, cells with Meis1 knockdown failed to differentiate into horizontal cells. Taken together, I demonstrate that Meis1 transcription factor regulate the expression of Foxn4 expression and horizontal cell lineage development in the vertebrate retina via their interactions with CR4.2. These findings provide new insights into molecular mechanisms that govern gene regulation in retinal progenitors and vertebrate retinal cell development.
Subject
(authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3869
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xii, 110 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Mohammed Monirul Islam
Subject
(authority = ETD-LCSH)
Topic
Retina--Metabolism
Subject
(authority = ETD-LCSH)
Topic
Retina--Physiology
Subject
(authority = ETD-LCSH)
Topic
Transcription factors
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000065161
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T39P30KJ
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
Islam
GivenName
Mohammed
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-04-04 22:34:17
AssociatedEntity
Name
Mohammed Islam
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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