# Temporal control of cell patterning, signaling, and movement in early embryos

> **NIH NIH R35** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2022 · $623,119

## Abstract

Regulation of gene expression along the dorsal-ventral (DV) axis of Drosophila embryos serves as a 
paradigm of developmental patterning. Comparative studies of cis-regulatory elements that 
support expression along the DV axis from many research groups have made it clear that 
combinatorial input into enhancers by multiple transcription factors drives distinct 
spatial-outputs of gene expression. A pivotal regulator of this patterning process is the 
maternally-provided transcription factor Dorsal (Dl), homolog of NFKB. Dl functions as 
 a morphogen to activate target gene expression in a concentration-dependent manner along 
 the DV axis, contributing to the initiation of zygotic gene expression at the 
maternal-to-zygotic transition (MZT). Using live imaging, we quantified the Dl gradient in embryos 
and found, surprisingly, that levels change not only in space but also build in time. Our 
focus during the previous funding period was to study the impact of these Dl dynamics on target 
gene expression using quantitative approaches involving analysis of live imaging or fixed embryo 
time-series data to provide insight. In the current proposal, we follow three new and exciting 
directions, which relate to the timing of cell actions in early embryos and arose as a result of 
the previous work. Project 1 involves studying how broadly-expressed activators and repressors 
cooperate to control the onset of zygotic gene expression during the MZT. We hypothesize that 
broadly-expressed repressors are equally important to pioneer activators in the control of 
chromatin accessibility and thereby also regulate initiation of zygotic gene expression. Project 2 
focuses on dissecting the function of short-transcripts for long genes that are expressed 
specifically in the early syncytial embryo. We hypothesize that these short transcripts act to 
regulate timing of cell signaling pathway activation by functioning as dominant-negative variants 
of signaling molecules. Project 3 focuses on identifying the mechanism by which FGF signaling 
regulates adherens junctions (AJs) and their interaction with the actin cytoskeleton to contribute 
to the first epithelial-to-mesenchymal transition (EMT) in embryos; in particular, to understand 
how a degron associated with one FGF ligand, Pyramus, limits signaling time. The overarching goal 
of the proposed research program is to understand how the timing of these cell activities - 
patterning, signaling, and movement - are controlled in developing Drosophila embryos 
and to provide general insights applicable to higher animals. While many studies have focused on 
spatial outputs of gene expression, less is known about the temporal dynamics of patterning. 
Drosophila embryos are a tractable system to study MZT as it occurs in 3-4 hours, in 
contrast to taking days in preimplantation mammalian embryos. The Drosophila embryo is 
also amenable to live in vivo imaging and tracking analyses making it well-suited to the study of ...

## Key facts

- **NIH application ID:** 10445335
- **Project number:** 5R35GM118146-07
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Angelike Stathopoulos
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $623,119
- **Award type:** 5
- **Project period:** 2016-08-11 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445335

## Citation

> US National Institutes of Health, RePORTER application 10445335, Temporal control of cell patterning, signaling, and movement in early embryos (5R35GM118146-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445335. Licensed CC0.

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