Date of Award

Spring 2023

Degree Name

Bachelor of Science

Major

Biology

First Advisor

Robert J. Fleming

Second Advisor

Heather Bennett

Third Advisor

Kent D. Dunlap

Abstract

The Notch pathway is a highly conserved signaling system required for numerous developmental processes and tissue renewal and maintenance later in life. Much of the intracellular workings of the Notch signaling system have been uncovered, but the exact functions of specific extracellular regions of the Notch receptor remain largely a mystery. The extracellular domain of Notch contains 36 cysteine-rich epidermal growth factor-like repeats (EGFr); the functional significance of only a small subset of these repeats have been characterized. The Abruptex domain, which maps to EGFr 24-29, houses a plethora of missense mutations that display Notch hyperactivity. The nature of Abruptex hyperactivity is particularly puzzling due to the complex complementation patterns exhibited by the alleles in this region. To determine the mechanisms behind Abruptex hyperactivation of Notch, the Serrate alleles Bsp tom A41, Bd B16, and Ser374568 A5 were expressed under the control of the ptcGal4 promoter at various temperatures in a wild-type, AxE2, and Ax9B2 background. These Serrate alleles have varying abilities to participate in trans-activation and cis-inhibition with Notch. Through the phenotypic analysis of wing morphology, it was revealed that AxE2 and Ax9B2 have differing cis-inhibitory capabilities. AxE2 appears to have a reduced affinity for cis-inhibition by Serrate alleles, while Ax9B2 appears to have an increased sensitivity to cis-inhibition by Serrate alleles.

Comments

Senior thesis completed at Trinity College, Hartford CT for the degree of Bachelor of Science in Biology.

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