Undergraduate Honors Theses

Thesis Defended

Spring 2017

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Michael Klymkowsky

Second Advisor

Brian DeDecker

Third Advisor

Bilge Birsoy

Fourth Advisor

Harrison Carpenter

Abstract

Of the approximately 20,000 genes in the human genome, about 6,000 have unknown or poorly characterized function. Tumor protein p63 regulated 1-like (TPRG1l) is one of those genes with no functional data. TPRG1L is expressed during embryonic development and adulthood with strongest expression in the brain. It is implicated in carcinogenesis because its gene expression is activated by tumor regulators p63/73. To elucidate TPRG1L function during embryogenesis, CRISPR-Cas9 genome editing system was utilized to induce Tprg1l mutations in Xenopus laevis. Embryos injected with Tprg1l sgRNA and Cas9 mRNA displayed axis formation and convergent extension defects suggesting that Tprg1l mutants may have dysregulated Wnt signaling. The Wnt signaling pathway is an evolutionarily conserved pathway that is critical for proper head development, dorsoventral and anteroposterior axis establishment, and planar cell polarization. Since Wnt responsive genes are repressed by p63/p73 factors that activate Tprg1l expression, I hypothesized that TPRG1L may also regulate Wnt signaling. Tprg1l mRNA overexpression displayed axis deformities as well as convergent extension defects consistent with disruption of Wnt signaling. TPRG1L has an inositol polyphosphate 5-phosphatase domain that may reduce inositol polyphosphates that are necessary for normal Wnt signaling. This observation together with the results of loss and gain of function experiments suggest that TPRG1L may be a novel inhibitor of the Wnt signaling pathway.

Available for download on Thursday, April 12, 2018

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