Date of Completion

Spring 5-10-2024

Thesis Advisor(s)

Jianzhong Yu

Honors Major

Physiology and Neurobiology

Disciplines

Cancer Biology | Developmental Biology

Abstract

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of the Hippo pathway is less understood. This screening project attempts to identify novel upstream regulators of the Hippo pathway, specifically genes located on the X chromosome of Drosophila, through a forward genetic screen for overgrowth phenotypes. Random point mutations were induced through EMS treatment, and a merlin mutant background increased the sensitivity of the screen. After candidates were identified and validated, Diap1 levels were examined in third-instar larvae eye discs to determine the mutation’s impact on the Hippo pathway. A total of five overgrowth candidates were identified, and one was validated through reproducibility tests after establishing stocks. Diap1 staining suggests a role of the candidate mutation in regulating Hippo signaling. Future directions include mapping and characterizing the candidate mutations.

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