Tube formation is a nearly ubiquitous process required in metazoans to construct the thoroughfares through which the various liquids and gases that sustain life are transported. The high conservation of molecules and mechanisms that underlie development suggests that studies of tube formation in simple systems will provide paradigms for related processes in higher animals. This application focuses on the formation of two different tubes in the Drosophila embryo: the trachea, which forms an elaborate tubular network that carries oxygen to target tissues throughout the organism, and the salivary duct, which forms a simple Y-shaped tube that transports salivary gland secretions to the mouth. Both tubes depend on two transcription factors for their formation: trachealess (trh), which encodes a bHLH-PAS transcription factor, and ribbon (rib), which encodes a nuclear BTB protein with homology to the DNA-binding domains of the """"""""pipsqueak"""""""" family of transcription factors. In trh mutants, both the trachea and salivary duct fail to form tubes; the primordia for both tissues remain on the embryo surface at their site of origin failing to undergo any of the movements of tube morphogenesis. In rib mutants, only certain branches of the trachea fail to form and the salivary duct cells internalize but form short irregular tubes. Morphological studies of tube formation in the trachea and salivary duct suggest that although these tubular organs require both trh and rib, they form tubes by very different cellular mechanisms. Tracheal tubes form through cell invagination followed by directed migration of subsets of cells that form the various component branches. Duct tubes form by a """"""""wrapping"""""""" mechanism coupled with extensive cell rearrangements and shape changes. Our goal is to learn how TRH and RIB contribute to different aspects of tube morphogenesis, and to learn what events are shared among tubes that form by seemingly different cellular mechanisms. We will detail the cellular events that accompany different stages of tube morphogenesis in both tissues using a variety of microscopic techniques including confocal imaging of both fixed and living tissues. We will identify and characterize the roles of downstream target genes regulated by TRH and/or RIB in the trachea and salivary duct. We will learn how these downstream genes coordinate their activities to build both simple tubes and elaborate tubular networks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012873-09
Application #
7248803
Study Section
Genetics Study Section (GEN)
Program Officer
Burgoon, Penny W
Project Start
1999-02-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
9
Fiscal Year
2007
Total Cost
$387,569
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
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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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