# Formation of the Drosophila salivary gland

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $603,002

## Abstract

The FoxA family of winged-helix DNA-binding transcription factors (TFs) play major roles in the
development of many organs in vertebrate embryos. In some cases, they are proposed to be
determinants of specific cell fates because they are expressed early and continuously in forming
organs, and they are capable of what has been referred to as “pioneer” function – the ability to
bind their target motifs even in closed chromatin, whereupon they can “open” that chromatin to
make it accessible to other key tissue-specific “settler” TFs. Combined, the pioneer and settler
TFs activate expression of the genes controlling tissue morphogenesis, specialization and
homeostasis through their sequence-specific interactions with the corresponding target gene
enhancers. As with the vertebrate FoxA TFs, the single FoxA orthologue in Drosophila, known
as Fork head (Fkh), plays major roles in the formation of multiple organs and in controlling the
survival, morphology and physiology of the salivary glands (SG). The relative simplicity of the
Drosophila embryonic SG, the non-redundancy in Fkh function, the short development time, ex
utero development, and the huge armamentarium of excellent genetic tools make this an ideal
model system for testing current models for vertebrate FoxA protein function, for uncovering the
mechanisms by which FoxA proteins coordinate morphogenesis with tissue-specific
physiological specialization, and for finding and characterizing the downstream effectors that
directly impact overall organ architecture and organ placement.
In Aim 1, we propose to learn how Fkh works with two other early-expressed SG TFs – Sage
and Senseless (Sens) – to regulate expression of the salivary gland “secretome”. Based on
earlier findings, these studies will challenge the notion that Fkh has the same pioneering
function that has been proposed for the vertebrate FoxA TFs. In Aim 2, we propose to discover
and characterize the partner SG TFs and downstream effectors that mediate the FoxA-driven
morphological events that transform the two-dimensional salivary gland primordia into three
dimensional internalized epithelial secretory organs. These studies will be among the first to
reveal how FoxA proteins partner up to drive the morphological changes that underlie tissue
development. In Aim 3, we characterize three Fkh morphogenetic targets that help coordinate
the abundance, localization and activities of two major players in tissue remodeling – non-
muscle Myosin II and the sub-apical transmembrane protein Crumbs. As new targets are
discovered (through the earlier aims), we will also determine where, when and how newly
discovered morphogenetic players contribute to overall tissue architecture.

## Key facts

- **NIH application ID:** 10805482
- **Project number:** 5R01DE013899-22
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Deborah J Andrew
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $603,002
- **Award type:** 5
- **Project period:** 2001-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805482

## Citation

> US National Institutes of Health, RePORTER application 10805482, Formation of the Drosophila salivary gland (5R01DE013899-22). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10805482. Licensed CC0.

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