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TitleNuclear organization of mouse Hox cluster paralogs during mouse embryonic stem cell differentiation to neural stem cell
NamePanicker, Priya (author), Tischfield, Dr.Jay (chair), Shreiber, Dr. David (internal member), Serrano, Dr.Lourdes (outside member), Rutgers University, Graduate School - New Brunswick,
Degree Date2009-10
Date Created2009
SubjectBiomedical Engineering,
Homeobox genes,
Embryonic stem cells--Differentiation,
Neural stem cells
DescriptionIn this project we use Hox genes as a genetic tool to understand how nuclear architecture regulates cell differentiation during embryonic development. Hox genes come under the category of homeobox genes, a highly evolutionarily conserved group of genes with an important role during embryogenesis. Hox genes are located on 4 distinct chromosomes, in cluster paralogs (HOX A, B, C, D). Each individual cluster contains up to 13 homologous genes and corresponding genes on different clusters (e.g., HoxA13, HoxD13) exhibit varying degrees of functional redundancy. The position of a gene in the cluster is related to its spatiotemporal pattern of expression along the anterior-posterior axis of the embryo. The coordination of the spatiotemporal expression of equivalent paralog group genes on different clusters/chromosomes is coordinated is still not known. Our primary hypothesis is that nuclear architecture defines a regulatory framework of Hox cluster loci in the nucleus when the Hox cluster transcription is activated and maintained. We did a comparative analysis on the Hox cluster nuclear architecture in mouse embryonic stem cells (ESCs) and fibroblast growth factors (FGF) - induced differentiation to neural stem cells (NSC). We show for the first time that Hox gene expression is induced by FGF treatment in vitro simultaneously in the four Hox cluster. Using three-dimensional confocal fluorescence microscopy, FISH and computational techniques, we mapped the position of Hox gene cluster paralogs in individual nuclei of both cell types. We did not observe nuclear colocalization of Hox heterologous cluster in NSC. However, we observe that heterologous clusters tend to occupy similar nuclear domains in NSC, which may favor undetected long-range gene interactions. Nevertheless, our results indicate that Hox gene cluster nuclear three-dimensional organization is neither random nor correlated to the changes in nuclear volume and shape that parallel cell differentiation.
NoteM.S.
NoteIncludes bibliographical references (p. 53-55)
Noteby Priya Panicker
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051888
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work