# Investigating how sequentially acting cues guide long-distance cell migration in vivo within embryos

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $357,975

## Abstract

SUMMARY
Collective cell migration is essential to the progression of normal embryonic development and organogenesis,
and is a tightly-regulated process that can involve the interplay between two or more signaling pathways to
drive forward movement of cell cohorts. Additionally, patterning an organ often requires selective apoptosis
and compensatory proliferation of cells. Errors in collective migration and cell death programs can have serious
consequences, including complete developmental arrest, abnormal organ function, and tumorigenesis. In this
proposed research plan, we will use the Drosophila embryonic caudal visceral mesoderm (CVM), a small
population of muscle precursor cells that undergo highly stereotyped directional movement, as a model for
collective cell migration and survival. As the longest migration of embryogenesis, CVM cells must receive input
via signaling cues from other cells in order to navigate the changing environment of the developing embryo.
We have previously determined an important role for FGF signaling as both chemotropic and survival cue, and
that FGF receptor is specifically expressed in a subset of migratory cells. However, loss of FGF signaling does
not completely ablate collective migration, suggesting the existence of additional, as-of-yet uncharacterized
cues. The objective of this study is to gain a comprehensive understanding of the spatiotemporally-regulated
cues that guide directional movement of the CVM, and subsequent survival or apoptosis of distinct subsets of
cells. Our central hypothesis is that FGF signaling cooperates with additional signaling cues in order to drive
forward movement and cell survival, and involves defining specialized subsets of cells within each CVM cohort
to promote spatial organization driving forward movement. To test this hypothesis, we will pursue the following
specific aims: (AIM 1) Investigate roles for spatially-localized genes within the migrating CVM collective in
promoting cell migration; (AIM 2) Investigate mechanism of CVM attraction to PGCs; and (AIM 3) Investigate
the relationship between BMP and FGF signaling in regulating CVM cell migration and survival. To accomplish
these aims, we will employ an innovative combination of established genetics and immunostaining techniques
with elegant optogenetics and in vivo live imaging approaches to manipulate and visualize migratory cells, as
well as quantify spatiotemporal activation of the cell death program. We believe this study is significant
because it would not only demonstrate a mechanism for signaling cross-talk in an emerging yet
poorly-characterized cell migration system, but considering the large number of functions and diseases
attributed to signaling pathways such as BMP and FGF, elucidating the interaction between multiple pathways
in the context of the genetically-tractable and conserved Drosophila model system has the potential to identify
more specific therapeutic targets. Therefore, this study will be impact...

## Key facts

- **NIH application ID:** 10071887
- **Project number:** 1R01HD100189-01A1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Angelike Stathopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,975
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071887

## Citation

> US National Institutes of Health, RePORTER application 10071887, Investigating how sequentially acting cues guide long-distance cell migration in vivo within embryos (1R01HD100189-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071887. Licensed CC0.

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