# Formation of the Drosophila salivary gland

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $559,459

## Abstract

The Drosophila salivary gland (SG) is an ideal model for revealing the molecular and cellular
events underlying formation and physiological specialization of epithelial tubular organs, such as
the lungs, kidneys, 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. We have
discovered four key transcription factors that play major roles in the morphogenesis and
physiological specialization of the SG, and we have identified many/most of their transcriptional
targets using genome-wide approaches. In this proposal, we explore how these proteins function
both independently and as part of larger complexes to regulate distinct aspects of epithelial tube
development. In Specific aim #1, we use genome-wide in vivo DNA binding assays to test our
model that the levels of expression of SG specific gene products is mediated through the
coordinate binding of three key transcription factors – Fkh, the Drosophila FoxA orthologue,
Sage, a less highly conserved bHLH protein expressed in only the SG, and Sens, a zinc-finger
transcription factor whose SG expression requires Fkh and Sage. We ask if CrebA, a bZip
transcription factor that increases secretory capacity, also boosts levels of SG target gene
expression directly or indirectly. We will identify binding sites for each protein, both in WT SGs
and in SGs mutant for each other transcription factor. The biological relevance of specific cis
acting sites will be validated in a representative subset of known target genes. These studies will
reveal if we have identified the major factors controlling SG gene expression, and tests
mechanistic models of enhancer organization and function in a system where the key major
players and their downstream targets are known and can be manipulated. In Specific aims #2
and #3, we focus on the Sage, Sens and CrebA – independent functions of Fkh in controlling
formation of epithelial tubes. We have identified Fkh target genes that when mutant disrupt
early stages of tube morphogenesis. We ask how the products of these early Fkh target genes
interface with membrane and cytoskeletal proteins to coordinate changes in cell shape and
arrangement during tube internalization. We further use the Fkh binding data from aim #1 to
identify additional key morphogenetic regulators.

## Key facts

- **NIH application ID:** 9960310
- **Project number:** 5R01DE013899-19
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Deborah J Andrew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $559,459
- **Award type:** 5
- **Project period:** 2001-02-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960310

## Citation

> US National Institutes of Health, RePORTER application 9960310, Formation of the Drosophila salivary gland (5R01DE013899-19). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960310. Licensed CC0.

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