miR-137 targets Myc to regulate Development and Tumor Growth in Drosophila eye model

miR-137 targets Myc to regulate Development and Tumor Growth in Drosophila eye model

Presenter(s)

Rad Padma

Comments

1:40-2:00, LTC Forum

Description

During organogenesis, the regulation of gene expression controls the fundamental cellularprocesses like cell proliferation, differentiation, and cell death. Among many gene regulatorymolecules, miRNA(s), a class of small non-coding RNAs, regulate more than one targetmRNA expression during development. To understand the molecular-genetic mechanism(s)regulating eye development, we employed a forward genetic screen to identify the miRNAinvolved in controlling patterning and growth in the Drosophila eye. We identified miR-137whose gain-of-function (GOF) in developing eye results in reduced eye phenotype and loss-of-function results in enlarged eye phenotype. We found that reduced eye phenotype isaccompanied with reduced expression domains of markers of retinal determination anddifferentiation and increased negative regulators of eye development like Wingless (Wg) andHomothorax (Hth). In the developing eye, Wg is known to block the progression of asynchronous wave of differentiation referred to as the Morphogenetic furrow (MF). The GOFof miR137 significantly downregulates the expression of dpp-lacZ, an MF marker. Usingbioinformatic approaches, followed by genetic experiments, we identified Myc as a target ofmiR-137 as the GOF of Myc can rescue reduced eye phenotype of miR-137 GOF or viceversa. Our data suggest a new role of miR-137 in targeting Myc in the developing eye todetermine eye size by regulating retinal- determination, -differentiation, and cellularhomeostasis. We tested GOF of miR-137 in RasV12 , scrib RNAi background, an establishedtumor model for oncogenic cooperation that results in neoplastic tumors. The GOF of miR-137 show a significant rescue of tumor phenotype in the eye along with a significantreduction in Myc levels. Our studies shed light on the role of miR-137 in tissue homeostasis,growth regulation, and development.

Publication Date

4-23-2025

Project Designation

Independent Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Scholarship; Scholarship

miR-137 targets Myc to regulate Development and Tumor Growth in Drosophila eye model

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