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.
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.
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|Fox, Rebecca M; Andrew, Deborah J (2015) Transcriptional regulation of secretory capacity by bZip transcription factors. Front Biol (Beijing) 10:28-51|
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|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|
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