# Development and maintenance of plantar skin

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $178,316

## Abstract

Abstract: The thickened epidermis of palmoplantar (sole and palm) skin expresses a
unique combination of structural proteins that contribute to its superior resistance to
biomechanical stress. PP skin is also hypo-pigmented when compared with adjacent skin,
is hairless and exhibits a high density of eccrine sweat glands (EG). Prior research
demonstrates that regional specific differentiation of the epidermis is imposed on
keratinocytes during embryonic/perinatal development but that once specified,
keratinocytes develop an intrinsic epigenetic memory of their site of origin. Grafting and
culture experiments suggest that this memory is incomplete, and that signaling from
orthotopic dermis sustains and augments appropriate PP differentiation, while signals
from heterotopic dermis can promote alternative differentiation. These studies have been
hampered by reliance on a limited set of markers. The work proposed here employs
genetically modified mice to create a comprehensive molecular description of sole-
specific epidermal differentiation by RNAseq and identify inductive signals from the
dermis that promote that differentiation during development. Inducible gain and loss of
function of genes that generate bi-dorsal and bi-ventral feet are used to explore the extent
to which the inductive signals that specify regional keratinocyte identity in the sole are
required to maintain site-specific epidermal differentiation in the adult. We also ask
whether manipulation of those signals in intact skin can provoke epidermis in other
regions of the body to adopt aspects of sole epidermal character. Successful completion
of this work will settle controversies about the relative weight of intrinsic keratinocyte
characteristics vs. ongoing inductive signaling from dermis in intact adult skin. It is
designed to provide insights that may lead to novel approaches to conferring superior
performance on patient skin that has been forced to assume load-bearing duties, for
example when leg amputation imposes this function on more proximal limb skin.

## Key facts

- **NIH application ID:** 10399418
- **Project number:** 5R21AR078511-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** BRUCE A MORGAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $178,316
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399418

## Citation

> US National Institutes of Health, RePORTER application 10399418, Development and maintenance of plantar skin (5R21AR078511-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399418. Licensed CC0.

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