# Morphogenetic mechanisms regulating directed cell migration required to form the vertebrate posterior body

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $332,319

## Abstract

PROJECT SUMMARY
Much of the vertebrate embryonic body forms from a recently discovered neuromesodermal progenitor cell
population located at the most posterior end of the early embryo, in a region called the Progenitor Zone (PZ).
The PZ gradually releases mesodermal cells that populate the somites (primarily muscle) as well as the neural
cells that form the spinal cord, until the complete anterior-posterior axis of the embryo has been established.
While the mechanisms controlling the differentiation of the neuromesodermal cells are increasingly
understood, how these cells regulate the completion of the epithelial to mesenchymal transition (EMT) and
directional migration from the PZ into the body largely remains a mystery, yet this process is essential for the
embryo to form its anterior-posterior axis correctly.
Based on our analysis of a zebrafish mutant that specifically disrupts the migration of mesodermal cells from
the PZ, we have identified a unique set of PZ-expressed Progenitor Cytoskeletal Regulatory Genes (PCRGs) that
we propose must be down-regulated for cells to complete the EMT and migrate from the PZ into the
presomitic mesoderm (PSM). Using a novel explant assay we recently developed that allows in vivo imaging of
the migrating cells at very high resolution, in Aim 1 we will determine how the PCRGs are used to regulate the
directional movement of cells into the PSM using a combination of gain and loss of function studies, as well as
examining how the PCRGs control Rho activity.
In Aim 2 we will determine how the posterior hox genes, which through unknown mechanisms control the
orderly movement of cells from the PZ into the embryonic body, specifically regulate cell movements using
our novel explant system to examine directional cell migration and protrusive activity of the hox-expressing
cells. We will test the hypothesis that the hox genes act to sustain the expression of the PCRGs, and thereby
regulate the timing of cell entry into the PSM.
Collectively, these studies will examine the premise that the migration of cells from the PZ into the PSM is
regulated by the action of the PCRGs and posterior hox genes, which acting together control the orderly
anteriorward migration of newly differentiating mesodermal cells, thus allowing the vertebrate embryonic
body to form with remarkable fidelity. With the ease of making transgenic lines that allow temporally
controlled expression of the PCRGs and hox genes as well as CRISPR mutant lines, combined with our
innovative explant system for high resolution imaging, zebrafish is an excellent system for understanding the
mechanisms that control the early formation of the vertebrate body.

## Key facts

- **NIH application ID:** 9982378
- **Project number:** 5R01GM079203-12
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David Kimelman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,319
- **Award type:** 5
- **Project period:** 2008-07-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982378

## Citation

> US National Institutes of Health, RePORTER application 9982378, Morphogenetic mechanisms regulating directed cell migration required to form the vertebrate posterior body (5R01GM079203-12). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9982378. Licensed CC0.

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