# Investigating the formation of spatial and directional patterns in the mammalian epidermis

> **NIH NIH F31** · PRINCETON UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary
The development of epithelial organs involves a complex interplay between epithelial-
mesenchymal interactions, cell fate induction, proliferation, and tissue polarity. In epithelial
organs, intercellular signaling and mesenchymal interactions specify the spatial patterns of
tubes, branches, and other specialized cell types. How these events are coordinated to
generate organs with precise and reproducible patterns, dimensions, and sizes remains poorly
understood. With recent advancements that allow patient-specific stem cells to be differentiated
into organs in a dish, how these forms arise has become increasingly important to resolve. The
goal of this proposal is to decipher how intercellular signaling, cell fate specification, and tissue
polarity coordinate morphogenesis of developing the skin epithelium. The mammalian skin,
which is decorated with spatially patterned, globally aligned hair follicles is an excellent system
to explore how polarized architecture is established in multicellular structures. Recently we
discovered an unexpected and novel collective cell behavior that directs morphological and cell
fate asymmetry in developing hair placodes. The polarization of initially circular hair placodes is
driven by dramatic cell rearrangements coordinated in a counter-rotational pattern of cell flows.
To generate the pattern of cell flow, spatial patterning of radial cell fates cooperates with planar
cell polarity to direct polarized cell neighbor exchanges through myosin-dependent junction
disassembly. Using a combination of live imaging, genetic mosaics, biophysical manipulations
and transcriptional profiling, the following proposal will test the hypothesis that differences in
motility, contractile forces on intercellular junctions and cell-cell adhesion between inner and
outer placode cells drive counter-rotational cell movements during placode polarization.
Successful completion of these aims will provide an integrated view of how cell signaling, cell
fate specification, polarity and adhesion cooperate to generate a novel mode of tissue
morphogenesis. We anticipate that counter-rotating cell rearrangements may be in fact be
widespread in epithelial organs, polarizing a wide array of branched and tubular structures.
Thus, our findings are likely having a broad impact on the fields of regenerative medicine and
tissue engineering.

## Key facts

- **NIH application ID:** 9988162
- **Project number:** 5F31AR074246-03
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Liliya Leybova
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988162

## Citation

> US National Institutes of Health, RePORTER application 9988162, Investigating the formation of spatial and directional patterns in the mammalian epidermis (5F31AR074246-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9988162. Licensed CC0.

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