# Transcriptional control of collective cell migration

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2020 · $125,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Critical physiological and pathological processes, such as wound healing, blood vessel formation and cancer
metastasis, rely on directed collective cell migrations, whereby groups of cells collectively polarize and move
together in an orderly fashion. The ability of cell collectives to migrate directionally is determined in part by the
tissue-specific transcriptional inputs that define the complement of expressed genes and thus their competence
to migrate. The long-term goal of this project is to understand how tissue-specific transcription regulators
control the basic cellular processes underlying directed collective cell migration. To this aim, the simplified
embryos of a chordate species, the ascidian Ciona intestinalis, will be used to study the migration of pre-
cardiac mesoderm cells, called “trunk ventral cells” (TVCs). The TVCs provide the simplest possible model of
directed collective cell migration in live embryos. On each side of the embryo, only two cells migrate together
and display a clear Leader-Trailer polarity aligned with the direction of migration: the leader TVC displays a
broad leading edge and more conspicuous protrusions than the trailer. It was previously established that Mesp,
Fibroblast growth factor (Fgf) signaling and FoxF transcriptional inputs determine the ability of TVCs to
migrate. Moreover, TVCs migrate strictly between the endodermal and ectodermal germ layers, a hallmark of
mesodermal cardiac progenitors. It was determine that these surrounding tissues contribute to canalizing
TVCs' innate motility towards collective polarity and directed migration. The goal of the proposed research is to
understand how transcriptionally-controlled intrinsic TVC properties interface with extrinsic signals to
determine collective polarity and directed migration in the embryo. Preliminary studies suggested that the gene
encoding the discoidin domain receptor (Ddr) is upregulated by Mesp, FGF and FoxF transcriptional inputs in
the TVCs, where it promotes adhesion to the epidermis. Using newly developed quantitative imaging methods,
the detailed mechanisms controlling Ddr expression, localization and activity will be analyzed. The hypothesis
that a cell-autonomous antagonism between Ddr and vascular endothelial growth factor receptor (Vegfr)
signaling positions the migrating TVCs between the epidermis and endoderm will be tested. Preliminary
observations suggest that Ddr promotes adhesion to the epidermis by regulating vesicle trafficking. The
hypothesis that Ddr acts in Rab4/Rab11-positive endosomes to promote the recycling of integrins to the plasma
membrane will be tested. Finally, the functions of regulated candidate effectors of collective migration will be
studied extensively using TVC-specific CRISPR/Cas9-mediated loss-of-function assays and high-content
phenotypic analyses. A provisional model of the biomolecular network controlling the subcellular processes
underlying TVC behavior will be built. ...

## Key facts

- **NIH application ID:** 10136229
- **Project number:** 3R01GM096032-09S1
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Lionel Christiaen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $125,000
- **Award type:** 3
- **Project period:** 2010-09-23 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136229

## Citation

> US National Institutes of Health, RePORTER application 10136229, Transcriptional control of collective cell migration (3R01GM096032-09S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136229. Licensed CC0.

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