Date of Award

Spring 5-2015

Degree Type

Masters Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Sandra M. Leal

Committee Chair Department

Biological Sciences

Committee Member 2

Glen Shearer, Jr

Committee Member 2 Department

Biological Sciences

Committee Member 3

Alex S. Flynt

Committee Member 3 Department

Biological Sciences

Abstract

Stem cell niches are highly organized and specialized microenvironments located within specific tissues of both vertebrate and invertebrate organisms [1]. In Drosophila melanogaster, three distinct stem cell niches have been identified within the ovary including the germline stem cell (GSC), follicle stem cell (FSC), and escort stem cell (ESC) niche. Recently, Fregoso-Lomas et al. [2] reported that Gurken/Epidermal Growth Factor Receptor (EGFR) signaling is modulated within posterior ovarian follicle cells by Midline (Mid). The mid gene encodes a T-box transcription factor protein that specifies cell fates in the developing heart [3][4], central nervous system [5][6], epidermis [7], and eye of Drosophila [8]. The Tbx20 gene represents the conserved vertebrate ortholog of mid. Experimental evidence suggests that Tbx20 regulates cell proliferation within the embryonic chamber of the mouse myocardium; Tbx20-/- null mice exhibit increased expression of Tbx2 with a concomitant decrease in N-myc-1 expression, a proto-oncogene. These disturbed signaling events induce hypoplasia [9].

The Leal lab undertook a genetic modifier screen and discovered that mid interacts with several genes implicated in the control of cellular proliferation including extramacrochaetae (emc)[8] and dFOXO[10]. In addition, the modENCODE consortium identified bric-a-brac-1 and bric-a-brac-2 (bab-1 and bab-2) as theoretical mid-interacting genes that encode proteins harboring a BTB/POZ-ZF domain in Drosophila. The BTB/POZ-ZF domain is associated with oncogenic activity in humans [11]. Towards meeting the aims of the Master’s Thesis research, we carried out: 1) loss-of-function (LOF) and gain-of-function (GOF) studies with mid and specific mid-interacting genes within developing egg chambers, 2) cellular proliferation assays, and 3) immunofluorescent studies. Taken together, these studies allowed us to decipher the functional collaboration of mid with either bab-2 or bab-1 as a regulator of cellular proliferation within stem cell niches and as a critical gene required for oogenesis.

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