Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye

Bibliographic Details
Main Author:	Tare, Meghana
Language:	English
Published:	University of Dayton / OhioLINK 2013
Subjects:	Genetics Developmental Biology
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=dayton1367288552

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-dayton13672885522021-08-03T05:22:46Z Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye Tare, Meghana Genetics Developmental Biology Complex network of genetic and molecular mechanisms governing the process of organogenesis have an important bearing on development of organisms. We are using an established model of Drosophila melanogaster commonly referred to as fruit fly in order to understand these mechanisms. We have used Drosophila eye to discern genetic hierarchy controlling the (i) event of axial patterning, and (ii) to study neurodegeneration in the developing eye. Axial patterning involves generation of dorsal-ventral (DV), anterior-posterior (AP) and proximal-distal (PD) axes in the organ primordium and is considered crucial for transformation of monolayer epithelium into a three dimensional organ. Any abnormalities in expression patterns of axial patterning genes may result in complete loss of organ. Drosophila eye develops from a default ventral state conferred by expression of genes Lobe (L) and Serrate (Ser). It has been found that antagonistic interaction of dorsal and ventral genes helps generation of midline or the equator which is essential for growth and differentiation of the eye field. Loss-of-function of L/Ser results in complete or loss-of-ventral eye depending on time axis involved. In a genetic modifier screen performed for search for modifiers of L mutant phenotypes, an E3 ubiquitin ligase, Cullin-4 (Cul-4) and GATA-1 transcription factor Pannier (Pnr) were identified. In the current study, we have characterized Cul-4, in promoting cell survival in the ventral domain of developing eye via downregulation of Wingless (Wg) signaling. Cul-4 also regulates JNK signaling to prevent cell death in the developing eye. We thus place the Cul-4 in the hierarchy of ventral genes involved in eye development. We also present the role of GATA-1 transcription factor Pnr in defining the dorsal eye margin boundary by suppressing the eye fate. Pnr downregulates retinal determination gene machinery via zinc finger transcription factor teashirt (tsh). We thus provide a novel mechanism involved in defining dorsal margins of the eye during early stages of organogenesis and an eye suppression function, as a late role of pnr in the developing eye. Identification and characterization of these genes in the dorsal and ventral domains of the eye may help enrich our understanding of the genetic hierarchy and the complex interactions of genes involved in axial patterning in the eye during organogenesis. Since the genetic machinery is highly conserved from flies to humans, these studies will have direct implications on higher vertebrates as well. Other than patterning and growth studies, Drosophila eye has been widely used to study genetic and molecular basis of neurodegeneration. A part of current study is to test the mechanisms involved in the neuronal cell death caused during the course of Alzheimer’s disease (AD). AD is caused due to accumulation of Aß-42 peptide which is a product formed because of incorrect cleavage of Amyloid Precursor Protein (APP). Accumulation of Aß-42 results in formation of amyloid plaques which eventually results into stress and the neuronal cell death. We have found that JNK signaling pathway is induced upon Aß-42 accumulation and causes cell death of the neurons in the brain. Our study provides a new mechanistic insight from the perspective of identifying the new targets of AD neuropathy. 2013-05-29 English text University of Dayton / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=dayton1367288552 http://rave.ohiolink.edu/etdc/view?acc_num=dayton1367288552 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Genetics Developmental Biology
spellingShingle	Genetics Developmental Biology Tare, Meghana Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
author	Tare, Meghana
author_facet	Tare, Meghana
author_sort	Tare, Meghana
title	Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
title_short	Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
title_full	Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
title_fullStr	Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
title_full_unstemmed	Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye
title_sort	genetic mechanisms involved in axial patterning and neurodegeneration in drosophila eye
publisher	University of Dayton / OhioLINK
publishDate	2013
url	http://rave.ohiolink.edu/etdc/view?acc_num=dayton1367288552
work_keys_str_mv	AT taremeghana geneticmechanismsinvolvedinaxialpatterningandneurodegenerationindrosophilaeye
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Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye

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