Semester

Fall

Date of Graduation

2019

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Shuo Wei

Committee Co-Chair

Jennifer Gallagher

Committee Member

Eric Tucker

Committee Member

Peter Mathers

Committee Member

Andrew Dacks

Abstract

Canonical Wnt signaling is a pathway that is critical for normal development and the progression of disease. The canonical Wnt signaling pathway was put together carefully by synthesizing decades of research. Over those decades, canonical Wnt signaling was found to be crucial for nearly all aspects of development, but of importance to this thesis, is a key regulatory factor for the development of the highly migratory multipotent stem cells, the neural crest. As our knowledge of the importance of canonical Wnt signaling grew, research is being conducted to further our understanding of how canonical Wnt signaling communicates with other signaling pathways. Over my Ph.D., we have provided new mechanisms for how canonical Wnt signaling cross-talks with Ephrin and Akt signaling. Here, I discuss how EphrinB signaling inhibits canonical Wnt signaling during neural crest induction and in human cell culture. Within that project, we found that the metalloproteinase ADAM19 protects ADAM13 during neural crest induction to inhibit EphrinB signaling, thus activating canonical Wnt signaling. I also discuss how Akt signaling is necessary for neural crest induction to activate canonical Wnt signaling. Within that project we found that the RNA-helicase DDX3 is required for Rac1 expression during neural crest induction to activate Akt signaling and thus activate canonical Wnt signaling. Finally, I discuss the impact of connecting canonical Wnt signaling with Ephrin and Akt signaling in neural crest, development, disease, and potential new discoveries and research.

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