Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for +publisher:"University of North Carolina" +contributor:("Weise Cross, Laura"). One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of North Carolina

1. Weise Cross, Laura. Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2.

Degree: Pathology and Laboratory Medicine, 2015, University of North Carolina

Smooth muscle cells (SMCs) play an important role in vascular development and disease. Vascular SMCs undergo profound changes in phenotype in response to environmental cues that aid in development and vascular repair, but perturbations in the process contribute to many cardiovascular diseases, including atherosclerosis, restenosis, and hypertension. Therefore, it is critical to determine the mechanisms that control their phenotype. We have previously shown that the small GTPase RhoA promotes SMC differentiation through an SRF-dependent mechanism, and the RhoA effectors mDia1 and mDia2 mediate this effect through actin polymerization-dependent localization of the myocardin-related transcription factors (MRTFs). The primary aim of this dissertation is to further dissect the contributions of mDia signaling to SMC phenotype in vivo and in the nuclear compartment of the cell. Using a Cre-based approach, we overexpressed a dominant-negative mDia variant specifically in SMCs in a mouse model. We determined that inhibition of mDia signaling impaired cardiac structure and normal vessel morphology in a subset of developing mice. Adult mice exhibited altered SMC marker gene expression and abnormal SMC migration, indicating that mDia signaling has roles in both SMC differentiation and migration. In vitro studies revealed that mDia variants that preferentially localized to the nucleus significantly enhanced SMC-specific transcription, while those that were less nuclear exhibited reduced SMC transcriptional activity. These observations were also recapitulated with other RhoA signaling genes, implicating a model whereby nuclear RhoA signaling promotes SMC differentiation. Finally, little is known about the mechanisms regulating the expression of the RhoA signaling gene program. Using DNase I hypersensitivity methods coupled to high-throughput sequecing, deletion and mutation analysis, and a transgenic LacZ approach, we present novel evidence that this signaling pathway, including mDia2, may be regulated in an SRF-dependent manner. Because RhoA signaling promotes SRF-dependent transcription, we hypothesize that this mechanism serves as an auto-regulatory feed-forward circuit to promote SMC differentiation. Advisors/Committee Members: Weise Cross, Laura, Mack, Christopher P., Burridge, Keith, Furey, Terrence, Homeister, Jonathon, Wolberg, Alisa.

Subjects/Keywords: Pathology; Cytology; Molecular biology; School of Medicine; Department of Pathology and Laboratory Medicine

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Weise Cross, L. (2015). Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b656650d-84e2-48f7-ac8b-4135ba45a063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Weise Cross, Laura. “Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2.” 2015. Thesis, University of North Carolina. Accessed January 16, 2021. https://cdr.lib.unc.edu/record/uuid:b656650d-84e2-48f7-ac8b-4135ba45a063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Weise Cross, Laura. “Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2.” 2015. Web. 16 Jan 2021.

Vancouver:

Weise Cross L. Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 16]. Available from: https://cdr.lib.unc.edu/record/uuid:b656650d-84e2-48f7-ac8b-4135ba45a063.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Weise Cross L. Regulation of Smooth Muscle Cell Phenotype by the RhoA Effectors mDia1 and mDia2. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:b656650d-84e2-48f7-ac8b-4135ba45a063

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.