During development, organ precursors are specified through a combination of localized transcription factors and signaling events. Cell growth, rearrangement and directed migration shape and position organs as they develop. Ultimately, cells within different organs acquire unique physiological adaptations that allow them to perform their specialized functions. Many of the molecular pathways that function during the development of specific organs are also required to maintain function in the adult structures. Failure to achieve and maintain specialized functions often leads to organ failure and degeneration, and is thus linked to several human diseases and birth defects. To learn how organs form and acquire their unique physiological adaptations, we are using a simple model: the Drosophila salivary gland, which is the largest secretory organ in the animal. It is comprised of two paired secretory tubes, which synthesize and secrete large amounts of proteins, and smaller duct tubes, which connect the secretory tubes to the mouth and serve as a conduit for the salivary gland secretions. In previous work, we and others have identified the localized transcription factors and signaling pathways that determine where the salivary gland will form, that control the number of cells recruited to a salivary gland fate and that distinguish among the major cell types in this organ. We have also identified six early expressed transcription factors that have profound effects on salivary gland morphology and physiology. In this application, we propose to (1) identify the downstream targets of the six transcription factor genes that are expressed in the early salivary gland and are key to gland morphogenesis and physiology;(2) to determine the relative contributions of cell shape change and cell rearrangement to tube formation;and (3) determine how surrounding tissues contribute to the final correct placement of the salivary gland.
In aim 1, we will use whole mount in situ hybridization to determine which of 193+ known salivary gland genes are regulated by each of the six transcription factor genes.
In aim 2, we will use live imaging of marked cells to determine how much cell rearrangement normally occurs during tube invagination and elongation, and we will characterize a key subset of the transcriptional targets of the genes that mediate cell shape change and rearrangement.
In aim 3, we will characterize signaling pathways necessary for the salivary gland to navigate to its correct final position.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013899-10
Application #
7840519
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Burgoon, Penny W
Project Start
2001-02-01
Project End
2011-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
10
Fiscal Year
2010
Total Cost
$370,302
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
Chung, SeYeon; Kim, Sangjoon; Andrew, Deborah J (2017) Uncoupling apical constriction from tissue invagination. Elife 6:
Manning, Lathiena; Sheth, Jinal; Bridges, Stacey et al. (2017) A hormonal cue promotes timely follicle cell migration by modulating transcription profiles. Mech Dev 148:56-68
Wells, Michael B; Villamor, Jordan; Andrew, Deborah J (2017) Salivary gland maturation and duct formation in the African malaria mosquito Anopheles gambiae. Sci Rep 7:601
Hanlon, Caitlin D; Andrew, Deborah J (2016) Drosophila FoxL1 non-autonomously coordinates organ placement during embryonic development. Dev Biol 419:273-284
Fox, Rebecca M; Andrew, Deborah J (2015) Changes in organelle position and epithelial architecture associated with loss of CrebA. Biol Open 4:317-30
Wells, Michael B; Andrew, Deborah J (2015) ""Salivary gland cellular architecture in the Asian malaria vector mosquito Anopheles stephensi"". Parasit Vectors 8:617
Hanlon, Caitlin D; Andrew, Deborah J (2015) Outside-in signaling--a brief review of GPCR signaling with a focus on the Drosophila GPCR family. J Cell Sci 128:3533-42
Fox, Rebecca M; Andrew, Deborah J (2015) Transcriptional regulation of secretory capacity by bZip transcription factors. Front Biol (Beijing) 10:28-51
Andrew, Deborah J; Yelon, Deborah (2015) Editorial overview: Developmental mechanisms, patterning and organogenesis. Curr Opin Genet Dev 32:v-viii
Chung, SeYeon; Hanlon, Caitlin D; Andrew, Deborah J (2014) Building and specializing epithelial tubular organs: the Drosophila salivary gland as a model system for revealing how epithelial organs are specified, form and specialize. Wiley Interdiscip Rev Dev Biol 3:281-300

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