# Embryonic Cell Recognition: Specificity Determinants

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $331,005

## Abstract

Summary: Embryos begin development by forming a simple epithelium. Cells fated to become
connective tissue then undergo an epithelial-mesenchymal transition (EMT) to leave that early
epithelium and populate the interstitial regions of the embryo. This project seeks to understand
how the EMT works, specifically how the cells de-adhere from the epithelium, how they become
motile to leave the epithelium, and how they invade through the basement membrane beneath
the epithelium. Previous work identified the transcriptional subcircuits of the gene regulatory
networks responsible for controlling the EMT. In the model system studied, each of the three
EMT components – de-adhesion, motility, and invasion – are driven by distinct subcircuits of
transcription factors. The goal of the project is to identify and functionally understand the
effector molecules that are directly regulated downstream of the transcription factors in the
subcircuits. Thus, the three aims of the project are: 1) What are the effector molecules,
controlled by the de-adhesion subcircuit, that initiate and conduct the deadhesion from the
epithelium, and how do they function? 2) What are the effector molecules, controlled by the
motility subcircuit, that initiate the motility necessary to move the nascent mesenchymal cell out
of the epithelium and through the basal lamina? And, 3) What are the effector molecules, driven
by the invasion subcircuit, that are necessary to provide access through the basement
membrane for the nascent mesenchyme cells. RNA-seq databases of those targeted cells at
different time points of the EMT were obtained, and also RNA-seq databases of the same cells
following the same temporal trajectories, but after knockdown of transcription factors in the
subcircuits, were obtained to provide a group of candidate effector molecules for the
experiments. Three different assays were developed for direct analysis of control and perturbed
(knockdowns) of the candidate molecules in an effort to identify participants in controlling the
de-adhesion, motility onset, and invasion. In addition to wanting to understand how these three
EMT components function in the model system the findings will be pertinent to understand how
EMTs operate with high fidelity in embryos to avoid birth defects such as cleft palate. And, the
data will be useful to understand progression of disease states where the invasive property
similar to normal embryonic cells, is co-opted by cells as they develop metastatic properties.

## Key facts

- **NIH application ID:** 9922946
- **Project number:** 5R01HD014483-38
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** DAVID MCCLAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $331,005
- **Award type:** 5
- **Project period:** 1980-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922946

## Citation

> US National Institutes of Health, RePORTER application 9922946, Embryonic Cell Recognition: Specificity Determinants (5R01HD014483-38). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9922946. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*