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Uncovering new roles for the FoxA pr...

Abrams, Elliott W.

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Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development./
Author:	Abrams, Elliott W.
Description:	214 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1625.
Contained By:	Dissertation Abstracts International65-04B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3130631
ISBN:	049677879X

Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development.
Abrams, Elliott W.

Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development. - 214 p.

Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1625.

Thesis (Ph.D.)--The Johns Hopkins University, 2004.

The Drosophila salivary gland is an excellent system to study organ development and function. The gland is a simple tube made up of a single layer of large epithelial cells and much is known about its specification. The homeotic complex composed of Sex Combs Reduced, Extradenticle, and Homothorax specify the salivary gland early in embryonic development and are required for the expression of the early transcription factors Fork head (Fkh) and CrebA. Fkh is critical for invagination of the gland and is essential for secretory cell survival. Not much is known about the role of CrebA in the salivary gland, although CrebA mutants may affect the integrity of the epithelium, and thus can influence its final shape. During the course of my thesis work, I investigated the roles of Fkh and CrebA in the development and function of the salivary gland. I found that CrebA is important in the activation of at least 30 early secretorty pathway component encoding genes (SPCGs) in the salivary gland and, furthermore, CrebA has a direct role in enhancing secretory function in the salivary gland. In addition to functioning in the salivary gland, CrebA plays a role in the formation of the larval cuticle through the activation of tested SPCGs in the embryonic epidermis. In addition to Fkh's role in maintaining SPCG expression, I have identified two targets of Fkh, which may, in part, contribute to the morphological phenotype associated with fkh loss of function mutations. These targets are homologous to the genes that encode the mammalian alpha-subunit of prolyl 4-hydroxylases (PH4alpha), which are important in modifying the extracellular matrix. To better understand Fkh's mechanism of regulating PH4alphaSG1 and PH4alphaSG2, I generated transgenic reporter lines and mutate potential FKH binding sites (which I confirmed using electrophoresis gel mobility shift assays). These experiments indicate that Fkh is important in directly initiating but not maintaining PH4alphaSG2 expression and only indirectly controls PH4alphaSG1 expression both early and late. From these results, I further identified a potential downstream target of Fkh, Sage, a basic helix-loop-helix transcription factor, which may be responsible for maintaining expression of PH4alphaSG1 and PH4alphaSG2.

ISBN: 049677879XSubjects--Topical Terms:

1017686
Biology, Cell.

Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development.
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245 1 0 $a Uncovering new roles for the FoxA protein Fkh and the BZip protein CrebA in Drosophila organ development.
300 $a 214 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1625.
500 $a Adviser: Deborah J. Andrew.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2004.
520 $a The Drosophila salivary gland is an excellent system to study organ development and function. The gland is a simple tube made up of a single layer of large epithelial cells and much is known about its specification. The homeotic complex composed of Sex Combs Reduced, Extradenticle, and Homothorax specify the salivary gland early in embryonic development and are required for the expression of the early transcription factors Fork head (Fkh) and CrebA. Fkh is critical for invagination of the gland and is essential for secretory cell survival. Not much is known about the role of CrebA in the salivary gland, although CrebA mutants may affect the integrity of the epithelium, and thus can influence its final shape. During the course of my thesis work, I investigated the roles of Fkh and CrebA in the development and function of the salivary gland. I found that CrebA is important in the activation of at least 30 early secretorty pathway component encoding genes (SPCGs) in the salivary gland and, furthermore, CrebA has a direct role in enhancing secretory function in the salivary gland. In addition to functioning in the salivary gland, CrebA plays a role in the formation of the larval cuticle through the activation of tested SPCGs in the embryonic epidermis. In addition to Fkh's role in maintaining SPCG expression, I have identified two targets of Fkh, which may, in part, contribute to the morphological phenotype associated with fkh loss of function mutations. These targets are homologous to the genes that encode the mammalian alpha-subunit of prolyl 4-hydroxylases (PH4alpha), which are important in modifying the extracellular matrix. To better understand Fkh's mechanism of regulating PH4alphaSG1 and PH4alphaSG2, I generated transgenic reporter lines and mutate potential FKH binding sites (which I confirmed using electrophoresis gel mobility shift assays). These experiments indicate that Fkh is important in directly initiating but not maintaining PH4alphaSG2 expression and only indirectly controls PH4alphaSG1 expression both early and late. From these results, I further identified a potential downstream target of Fkh, Sage, a basic helix-loop-helix transcription factor, which may be responsible for maintaining expression of PH4alphaSG1 and PH4alphaSG2.
590 $a School code: 0098.
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710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 65-04B.
790 1 0 $a Andrew, Deborah J., $e advisor
790 $a 0098
791 $a Ph.D.
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856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3130631