# Genetic and Cellular Mechanisms of Engrailed-1 Regulation and Function in Eccrine Sweat Gland Development

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $429,569

## Abstract

PROJECT SUMMARY
Eccrine glands are the major appendage of human skin and required for human thermoregulation. Despite their
importance, the cellular and molecular mechanisms of their development are poorly understood. This proposal
builds on our work implicating the transcription factor Engrailed-1 as a unique determinant and driver of eccrine
gland formation to define genetic and cellular mechanisms that induce the specification and differentiation of
eccrine sweat glands in the skin. Accordingly, the goals of this proposal are to identify the transcription factors
that directly modulate Engrailed1 expression during eccrine gland development (Aim1) and to define the
downstream Engrailed 1-dependent transcriptional program that then executes eccrine gland formation (Aim2).
This proposal integrates in vivo testing and high-throughput discovery of cellular and molecular components of
eccrine gland development using both newly generated and existing mouse models combined with mechanistic
dissection in cultured human skin cells and cross-validation between novel mouse and human single nucleus
transcriptomic datasets. As such, the proposed experiments will delineate the eccrine gland developmental
program, inform efforts to establish an in vitro system in which to study eccrine glands, and enhance
understanding of how ectodermal appendage fate and formation are established in the skin more broadly. From
a clinical perspective, our findings will provide a molecular blueprint for future studies to regenerate eccrine
glands in vivo and also offer novel points of intervention for repair of eccrine glands when these organs are
pathologically altered or damaged.

## Key facts

- **NIH application ID:** 10831049
- **Project number:** 5R01AR077690-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** YANA G KAMBEROV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,569
- **Award type:** 5
- **Project period:** 2020-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831049

## Citation

> US National Institutes of Health, RePORTER application 10831049, Genetic and Cellular Mechanisms of Engrailed-1 Regulation and Function in Eccrine Sweat Gland Development (5R01AR077690-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10831049. Licensed CC0.

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