# Molecular mechanisms underlying spatial patterning of mammalian skin

> **NIH NIH F32** · PRINCETON UNIVERSITY · 2020 · $65,310

## Abstract

Project Summary/Abstract
 The precise spatial and temporal patterning mechanisms that coordinate early embryonic development
represent a fundamental question in developmental biology. While such complex regulation is ultimately
determined at the genotypic level, the molecular mechanisms that connect genotype to phenotype remain
poorly understood. Elucidation of these mechanisms is of critical importance to human health, as errors in
these processes often lead to various developmental defects and diseased states. In this proposal, I will study
the formation of periodic pigment patterns (e.g., stripes and spots) to uncover the mechanisms by which
positional information is encoded in mammalian skin during embryogenesis. Periodic pigment patterns arise
from nonrandom developmental processes that are programmed to be spatially constrained, and thereby
represent an excellent model for understanding how a tissue acquires positional information. Specifically, I will
take advantage of the naturally evolved pigment pattern seen in the African striped mouse (Rhabdomys
pumilio), an emerging mammalian model system. I will combine a variety of genomic, transcriptomic, and
functional approaches to dissect the molecular and developmental mechanisms by which positional information
is acquired and interpreted in developing tissues, a long-standing question in developmental biology. First, I
will use novel chromatin profiling strategies coupled to functional approaches to identify the cis-regulatory
regions and their associated factors that control the spatially restricted expression of pigmentation genes.
Second, I will use single-cell RNA sequencing to reconstruct the developmental trajectories of the different cell
types of the embryonic skin and identify the signal(s) that establish the pattern boundary early in
embryogenesis. I will then modulate candidate gene expression to functionally test their effects on pigment
pattern formation. Taken together, this work will substantially advance our understanding of the mechanisms
that both establish and implement spatial patterns during early mammalian development. Through the
combined use of a novel mammalian model system and innovative, cutting-edge approaches, these
mechanisms will be investigated in a level of detail non-existent in the current literature. This work will generate
insights into the basic processes governing the development of mammalian skin, will provide a framework for
understanding the mechanistic basis of developmental disorders, and generate a more comprehensive
overview of the mechanisms regulating differential gene expression, a process at the forefront of various
human diseases and dysfunctions. Furthermore, the combined expertise of my advisor and co-advisor,
coupled with the abundant resources available at Princeton University (e.g., flow cytometry core and advanced
genomics core), will allow me to substantially expand my scientific training; from learning new skillsets (e.g.,
advanced ge...

## Key facts

- **NIH application ID:** 10066183
- **Project number:** 1F32GM139253-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Matthew Johnson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066183

## Citation

> US National Institutes of Health, RePORTER application 10066183, Molecular mechanisms underlying spatial patterning of mammalian skin (1F32GM139253-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066183. Licensed CC0.

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