Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Rui Yi, Ph.D.

Second Advisor

Jennifer Martin, Ph.D.

Third Advisor

Petger Schaberg, MA

Abstract

Transcription factor ∆Np63 is involved in stem cell maintenance and cell fate specification after mutations in the DNA binding region of p63 were found to be associated with multiple developmental abnormalities in humans. Deletions of the DNA binding region in mice produce severe phenotypic effects such as limb truncation and loss of the epidermis. Although the effects of p63 mutations are well documented, a mechanism by which p63 mutations produce these effects remained elusive. In this thesis I show that transcription factor ∆Np63 regulates components of the Wnt signaling pathway required for the specification and subsequent differentiation of skin lineages. p63 directly regulates Wnt10b, Wnt4, BMPR1B, and β-Catenin through enhancer recognition and transcriptional activation. ∆Np63 stimulates the Wnt signaling cascade by up-regulating several Wnt ligands as well as β-Catenin. Deletions of ∆Np63 enhancers for Wnt10b in vivo result in its reduced expression in the skin and associated appendages. Taken together, these findings reveal a role for p63 in regulating components of the Wnt signaling cascade important for epidermal fate specification.

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