Salivary gland formation in the developing Drosophila embryo provides a excellent system for understanding the molecular and cellular interactions required for tissue morphogenesis. Salivary gland cells participate in many of the movements characteristic of tissue differentiation, including nuclear repositioning, cell shape changes, invagination and tube formation. Only two major cell types comprise the Drosophila specialized for secretion, and the salivary duct cells, which are squamous epithelial cells organized into a polarized epithelium specialized for the passage of secretions. Once cells are specified to become salivary gland, they differentiate without further cell division; growth occurs simply by increasing the volume of individual cells. Many of the genes that control salivary gland fate determination and early morphogenesis have been identified and characterized. In previous work, we identified trachea-less (trh), a gene encoding a transcription factor required for tube formation in the salivary gland duct, trachea and filzkorper. In trh mutant embryos, each of these group of cells fails to invaginate to form their characteristic tubes. We have shown that trh is expressed in these tube-forming cells and have identified the molecules that control trh expression in the salivary gland duct. The goal of the research proposed here is to understand how the TRH transcription factor controls tube formation not only in the salivary duct but in other cells that also depend on its activity. We will first describe the cellular changes that occur during normal tube formation as a basis for assessing the relative contribution of trh and its downstream target genes in forming the tubes of the salivary duct and trachea. Second, we will identify these downstream genes and characterize their corresponding mutant phenotypes. Finally, we will study the molecular interactions between the TRH and the genes it regulates. The proposed work will link developmental genetics to the cell biology of organ assembly.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012873-05
Application #
6628526
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Burgoon, Penny W
Project Start
1999-02-01
Project End
2004-08-14
Budget Start
2003-02-01
Budget End
2004-08-14
Support Year
5
Fiscal Year
2003
Total Cost
$223,725
Indirect Cost
Name
Johns Hopkins University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Loganathan, Rajprasad; Lee, Joslynn S; Wells, Michael B et al. (2016) Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression. Dev Biol 409:234-250
Andrew, Deborah J; Yelon, Deborah (2015) Editorial overview: Developmental mechanisms, patterning and organogenesis. Curr Opin Genet Dev 32:v-viii
Ismat, Afshan; Cheshire, Alan M; Andrew, Deborah J (2013) The secreted AdamTS-A metalloprotease is required for collective cell migration. Development 140:1981-93
Maruyama, Rika; Andrew, Deborah J (2012) Drosophila as a model for epithelial tube formation. Dev Dyn 241:119-35
Chung, SeYeon; Chavez, Cy; Andrew, Deborah J (2011) Trachealess (Trh) regulates all tracheal genes during Drosophila embryogenesis. Dev Biol 360:160-72
Andrew, Deborah J; Ewald, Andrew J (2010) Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration. Dev Biol 341:34-55
Kerman, Bilal E; Andrew, Deborah J (2010) Staying alive: dalmation mediated blocking of apoptosis is essential for tissue maintenance. Dev Dyn 239:1609-21
Chung, SeYeon; Vining, Melissa S; Bradley, Pamela L et al. (2009) Serrano (sano) functions with the planar cell polarity genes to control tracheal tube length. PLoS Genet 5:e1000746
Andrew, Deborah J; Baker, Bruce S (2008) Expression of the Drosophila secreted cuticle protein 73 (dsc73) requires Shavenbaby. Dev Dyn 237:1198-206
Cheshire, Alan M; Kerman, Bilal E; Zipfel, Warren R et al. (2008) Kinetic and mechanical analysis of live tube morphogenesis. Dev Dyn 237:2874-88

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