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dc.contributor.advisorKim, Seonhee
dc.creatorRajavong, Kathleen
dc.date.accessioned2022-05-26T18:08:17Z
dc.date.available2022-05-26T18:08:17Z
dc.date.issued2022
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7674
dc.description.abstractCerebral palsy (CP) as a neurodevelopmental disorder that affects individuals’ movement, posture, and balance and occurs in every 2-3 out of 1,000 live births. Symptoms of CP can include seizures, hydrocephalus, impairment of the limbs, and learning disabilities. External contributors to CP are well known, but there are 80% of CP cases are idiopathic and in which no brain injury is reported. Recently, several genetic studies have shown that deleterious de novo mutations in CP patients may be implicated in CP pathogenesis. One such potentially deleterious de novo mutation of RhoB was identified in two CP patients. RhoB encodes for RHOB protein, a Rho GTPase that regulates the actin cytoskeleton. Biochemical and structural analyses of RhoB (S73F) protein suggested that the RhoB mutation generates a hyperactive form of RhoB. However, how the RhoB (S73F) protein may interfere with brain development and can contribute to CP is unknown. To determine whether RhoB (S73F) expression affects cortical development, we used in utero electroporations in mice to study the effect of RhoB (S73F) expression on cellular morphology, polarity, migration, and Golgi localization in the embryonic mouse model at E15.5 and P0, comparing it to a RhoB overexpression model as well as control. To address changes in cell morphology, we examined the cell size, shape, and volume of RhoB expressing cells using Imaris software. We show that RhoB overexpression and RhoB (S73F) expression cause detrimental changes in cell shape, polarity, and neuritogenesis. Furthermore, RhoB (S73F) expressing cells migrate less compared to RhoB overexpressing cells and control. Interestingly, we found that RhoB (S73F) expressing cells that did not migrate away from the ventricular surface still became neurons. To determine the effect of RhoB (S73F) expression on the subcellular environment, we examined the localization of the Golgi apparatus, and found the Golgi to be mislocalized and fragmented when RhoB (S73F) was expressed. Overall, this study shows that overexpression of RhoB is sufficient to cause changes in cell morphology, polarity, migration, and subcellular localization of the Golgi. Importantly, expression of RhoB (S73F) is distinct and unique from RhoB overexpression, causing more severe changes in cell size, shape, polarity, cell process number, and Golgi localization that result in failed neuronal migration. This data suggests the potential for genetic mutations to enact changes within the structure and function of cortical cells, which may contribute to the pathogenesis of CP.
dc.format.extent78 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectCellular biology
dc.subjectBiochemistry
dc.subjectNeurosciences
dc.subjectCerebral palsy
dc.subjectDe novo mutation
dc.subjectGolgi
dc.subjectNeuritogenesis
dc.subjectRho GTPase
dc.subjectRhoB
dc.titleEffects of the Cerebral Palsy-associated Mutation RhoB (S73F) in Cortical Development
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberThomas, Gareth
dc.contributor.committeememberGallo, Gianluca
dc.contributor.committeememberLangford, Dianne
dc.description.departmentCell Biology
dc.relation.doihttp://dx.doi.org/10.34944/dspace/7646
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreeM.S.
dc.identifier.proqst14767
dc.date.updated2022-05-11T16:08:33Z
dc.embargo.lift05/11/2023
dc.identifier.filenameRajavong_temple_0225M_14767.pdf


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