# Molecular and Cellular Control of Collective Cell Migration.

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $464,579

## Abstract

ABSTRACT
During embryonic development, cells often move in groups to assemble into tissues and
organs. They are guided by attractant gradients and coordinate their migration to move
in a directed manner. How attractant gradients are maintained and how cells in migrating
groups coordinate their movements is unclear.
To address these questions, we use the posterior lateral line primordium migration in
zebrafish as a model. The primordium is a group of about 100 cells, which express the
chemokine receptor Cxcr4 and follow a trail of Sdf1 chemokine. We have used this
system to show that the primordium generates an Sdf1 gradient across itself by
sequestering Sdf1 in its rear through the alternate Sdf1 receptor Cxcr7, a chemokine
scavenger receptor. In Aim 1, we will determine how Sdf1 levels are controlled by the
chemokine clearance receptor Cxcr7 using an Sdf1 signaling sensor that we developed.
The cells in the primordium also express cadherins and adhere to each other tightly. In
Aim 2, we will analyze the role of cadherins in coordinating collective migration and use
cadherin-based tension sensors to measure the tension forces between the cells in the
primordium. Our approach combines the optical accessibility of the zebrafish primordium
with quantitative imaging, embryonic and genetic manipulations, and novel sensors for
chemokine signaling and tension forces to provide a quantitative understanding of the
molecular and cellular mechanisms underlying collective cell migration. We anticipate
that our proposed studies will have two broad impacts on the field of cell migration. First,
they will provide a quantitative understanding of how attractant gradients are regulated.
Second, they will unravel the mechanics of cell-cell adhesion in a migrating tissue.
These insights are key to understanding major biological and medical problems including
defects in embryogenesis, organogenesis, and cancer metastasis.

## Key facts

- **NIH application ID:** 10357669
- **Project number:** 5R01NS102322-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Holger Knaut
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $464,579
- **Award type:** 5
- **Project period:** 2018-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357669

## Citation

> US National Institutes of Health, RePORTER application 10357669, Molecular and Cellular Control of Collective Cell Migration. (5R01NS102322-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10357669. Licensed CC0.

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