# Cell adhesion and cytoskeletal dynamics in the skin

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $711,835

## Abstract

Project Summary
Our global objective is to develop a molecular understanding of how epithelial stem cells undergo morphogenesis
and maintain homeostasis in mammalian skin, and to bring our research to a clinical setting. Our focus is on
how, in response to local developmental cues, skin stem cells remodel their cytoskeletal connections with
intercellular and cell-substratum junctions in order to generate and maintain tissues. Knowledge of the proteins
involved and their physiological roles in coordinating these cytoskeletal and adhesion dynamics are key to
understanding how skin epithelia form and are maintained and how cellular organization goes awry in
hyperproliferative skin disorders, including cancers. During skin development, a single layer of unspecified
epithelial progenitors can both stratify to form the surface barrier and also invaginate to form hair follicles (HFs).
As morphogenesis proceeds, resident stem cells are set aside so that in adult skin, self-renewing progenitors
maintain and repair the skin's barrier and fuel cyclical bouts of hair regeneration. In prior AR27883 research, we
showed that whether normal or malignant, all skin progenitors reside at epithelial-mesenchymal interfaces.
Progenitors utilize their underlying basement membrane to polarize and orient their spindle, balance growth and
differentiation and migrate. We have shown that in part, WNT-signaling is at the root of these polarized
cytoskeletal and adhesion dynamics. However, the epithelium must also sense and respond to cell crowding and
mechanical cues. How these signals intersect remain unclear. In the next 5 years, we'll address these critical
issues by: (1). Determining the governance and importance of cell density in tissue morphogenesis within the
epidermis and HFs. (2). Dissecting the roles of acto-myosin cytoskeletal regulators in tissue morphogenesis. (3).
Elucidating how the developing epidermis copes with poorly performing cells for the sake of tissue fitness and
how this changes once the stratified skin barrier is established. (4). Elucidating the role(s) of differential WNT-
signaling and mechanotransduction regulators within developing hair buds. We'll assess how signaling is sensed
in a polarized fashion and how cell density, tension and basement membrane production impacts the decision
to invaginate rather than evaginate. (5). Applying the knowledge gained in Aims 1-4 to dissect how and why
tissue morphogenesis and maintenance change in malignancy. To meet these aims, we'll combine a variety of
molecular and genetic approaches. During our R37-AR27883 MERIT Award, we developed live imaging to
interrogate cellular movements during skin development. We also pioneered a powerful in utero method to
efficiently and selectively compromise gene function in embryonic and adult skin to unveil the physiological
relevance of our findings. Finally, we adapted this technology to CRISPR/CAS, enabling us to conduct rapid
conditional knockouts in mice as well. O...

## Key facts

- **NIH application ID:** 10246415
- **Project number:** 5R01AR027883-43
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** ELAINE FUCHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $711,835
- **Award type:** 5
- **Project period:** 1980-12-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246415

## Citation

> US National Institutes of Health, RePORTER application 10246415, Cell adhesion and cytoskeletal dynamics in the skin (5R01AR027883-43). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246415. Licensed CC0.

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