# Tissue Patterning in living skin and organ ex

> **NIH NIH R37** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $520,132

## Abstract

Our long-term objective is to study the organizing principles that establish complex skin architectures
required for optimal skin functions. We have been using developing skin as experimental models because of
their distinct patterns which we use as a readout and their accessibility to experimentation. In the past, we
have taken an analytical approach to study the disruption of tissue patterns by altering expression levels of
different diffusible morphogens. Recent work from us and others have enlightened us that biophysical
processes also play integral roles in tissue patterning, and these roles have been under appreciated. We now
explore the ramifications of this novel understanding. Here we formulate a general hypothesis that tissue
patterning occurs by integrating molecular signaling and biophysical events. Newly expressed molecules on
cells lead to changes in the physical properties of cells and their surrounding matrix, causing disequilibrium
that drives biophysical processes to the next stage. Mechano-chemical coupling leads to new molecular
expression and so on, leading to the building of complex architectures. We will evaluate three key
morphogenetic events. First, the periodic patterning process that converts the skin from one morphogenetic
field to multiple skin appendage units. We suggest there are multi-layered controls. Tissue mechanics may
facilitate Turing patterning and help the propagation of the bud forming wave, while gap junctions may alter the
diffusion of intra-cellular second messengers to modulate the results of Turing patterns. Second, the formation
of stem cell-based skin appendage follicles in each unit. The margin of the feather bud shows planar cell
polarity, Tenascin C, and MMP14-FRET activity that drives bud margin epithelium to invaginate into the
dermis. Fate maps of stem cells and dermal papillae will be generated using singe cell RNA sequencing and
lineage tracing, and the results will be compared with that of hair follicles for key similarities. Third, adaptive
patterning in which adnexal structures such as blood vessels, nerves, dermal muscles, etc. are integrated back
to the skin to form one functional unit. We will use the assembly of the dermal muscle network as a paradigm
to explore these principles. The competence, specification and plasticity of dermal cell fates during this process
will be analyzed epigenetically using a SMA mechanosensor in living explants. By exploring the roles of tissue
mechanics in during tissue patterning of the skin, we can obtain a more holistic understanding of the self-
organizing processes in the development and regeneration of the skin. This knowledge will have significant
applications toward regenerative medicine in the future.

## Key facts

- **NIH application ID:** 10249265
- **Project number:** 5R37AR060306-12
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Cheng-Ming Chuong
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $520,132
- **Award type:** 5
- **Project period:** 2010-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249265

## Citation

> US National Institutes of Health, RePORTER application 10249265, Tissue Patterning in living skin and organ ex (5R37AR060306-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249265. Licensed CC0.

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