The Drosophila salivary gland (SG) is an ideal model for revealing the molecular and cellular events underlying formation and physiological specialization of secretory tubular organs, such as the pancreas, mammary and secretory glands of humans. The SG is a simple tubular organ that forms using the same morphogenetic changes as more complicated organs of higher animals, including changes in cell shape, adhesion and movement. The SG is also the largest secretory organ in the embryo providing an ideal model for how cells achieve high-level secretory capacity and how changes in capacity are coordinated with the expression of secretory content. Three key transcription factors are expressed in the specialized secretory cells of the SG from the onset of gland formation to the early stages of metamorphosis, as well as in the adult SG. Each transcription factor plays major roles in different aspects of SG biogenesis. The winged helix DNA binding protein Fork head (Fkh) is required for SG survival, for morphogenesis and for maintaining expression of itself and other SG-specific transcription factors. The bZip transcription factor CrebA increases secretory capacity by elevating the expression of protein components of secretory organelles and of secreted cargo. The bHLH DNA binding protein Sage is predicted to regulate expression of tissue-specific gene products based on its SG limited expression. Targets of each transcription factor are being discovered by microarray studies and in situ hybridization. These regulators and their targets are an excellent toolset for revealing the details of morphogenesis and the regulatory logic linking morphogenesis to functional specialization. The goals of this proposal are (Aim 1) to characterize the molecular machinery that coordinates apical constriction, a cell shape change required for the formation of many organs;
(Aim 2) to identify other key regulators that function with CrebA to achieve high-level secretory capacity in specialized secretory organs;
(Aim 3) to identify tissue- specific gene products to learn how their expression is coordinated with morphogenesis and acquisition of secretory capacity. This study is expected to provide new paradigms for how organ morphogenesis and physiological specialization are coupled during development.

Public Health Relevance

The salivary glands form by the same cell shape changes that form the neural tube of humans. Knowing how changes in cell shape are controlled will lead to better prenatal practices for the prevention of spina bifida and other neural tube defects. Also, since many human diseases are related to secretory dysfunction, learning how cells normally acquire high-level secretory capacity should reveal better treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013899-12
Application #
8289449
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Burgoon, Penny W
Project Start
2001-02-01
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
12
Fiscal Year
2012
Total Cost
$516,245
Indirect Cost
$198,399
Name
Johns Hopkins University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hanlon, Caitlin D; Andrew, Deborah J (2016) Drosophila FoxL1 non-autonomously coordinates organ placement during embryonic development. Dev Biol :
Fox, Rebecca M; Andrew, Deborah J (2015) Changes in organelle position and epithelial architecture associated with loss of CrebA. Biol Open 4:317-30
Fox, Rebecca M; Andrew, Deborah J (2015) Transcriptional regulation of secretory capacity by bZip transcription factors. Front Biol (Beijing) 10:28-51
Wells, Michael B; Andrew, Deborah J (2015) "Salivary gland cellular architecture in the Asian malaria vector mosquito Anopheles stephensi". Parasit Vectors 8:617
Andrew, Deborah J; Yelon, Deborah (2015) Editorial overview: Developmental mechanisms, patterning and organogenesis. Curr Opin Genet Dev 32:v-viii
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
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
Chung, Seyeon; Andrew, Deborah J (2014) Cadherin 99C regulates apical expansion and cell rearrangement during epithelial tube elongation. Development 141:1950-60
Abrams, Elliott W; Cheng, Yim Ling; Andrew, Deborah J (2013) Drosophila KDEL receptor function in the embryonic salivary gland and epidermis. PLoS One 8:e77618
Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika et al. (2013) Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA. Development 140:2160-71

Showing the most recent 10 out of 26 publications