# Specification and Molecular Control of the Hair Follicle Inductive Mesenchyme

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $371,309

## Abstract

Project Summary
The hair follicle (HF) is an excellent model system for studying the molecular cross-talk between
stem/progenitor cells and the microenvironment or niche. During embryonic HF formation epidermal
progenitors in hair placodes receive niche signals from dermal condensates (DC), precursors of the mature HF
mesenchyme, i.e. the dermal papilla (DP) and dermal sheath (DS). DP cells then act as niche for hair bulb
progenitors to coordinate continuous hair growth and for bulge/germ stem cells to launch a new hair cycle. The
role of the DS during hair growth is unclear. During the hair cycle, a subset of DS cells was recently identified
that replenishes the DS and to some extent could contribute to the DP compartment when challenged by
repeated depilation-induced hair cycling. Importantly, isolated mature DP cells can induce new HF formation
after transplantation, a potential suggested for the DS as well, but incomplete cell tracing in grafts precluded
definitive interpretation. Several key questions remain unanswered: What is the developmental lineage
relationship between embryonic DC and mature DS and DP? What is the definitive HF induction capacity of
DS? What are essential functions of the DS for initial HF growth? What are the molecular mechanisms that
control DS functions? By employing the extensive transcriptome-knowledge and genetic tools we recently
developed for embryonic DC and DP, we have now established with new preliminary data the conditions to
answer these questions and rigorously test the hypothesis that the DS constitutes a distinct
mesenchymal HF niche. With three dedicated Aims, we will determine the proliferative and clonal dynamics
with pulse-chase label retention experiments throughout morphogenesis and by lineage tracing of selectively
labeled single DC cells using established inducible Cre drivers and reporter mice. These studies will provide a
rigorous assessment of the differential proliferative proclivity and lineage relationship of the DS and DP. We
will then isolate for the first time simultaneously pure DS cells and DP using transgenic fluorescent reporter
mice, systematically define the unique DS molecular signature and use defined and traceable cell grafting
conditions to unequivocally determine their hair-inducing potential in established in vivo assays. Finally, we will
investigate the functional role of the identified DS transcription factor Satb2 and other novel DS signature
genes by in vivo gene ablation with our established inducible Cre lines. The results from these studies will
reveal the dynamics and functional relationship of DS and DP niches, definitively determine the capacity of DS
as hair-inductive mesenchyme, and achieve the first molecular insights into DS gene regulation. The ultimate
goal of this work is to expand our knowledge of stem cell regulation by the niche, which in the context of the HF
will be paramount for developing regenerative therapies to fully restore functional skin includi...

## Key facts

- **NIH application ID:** 9980791
- **Project number:** 5R01AR071047-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Michael Rendl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,309
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980791

## Citation

> US National Institutes of Health, RePORTER application 9980791, Specification and Molecular Control of the Hair Follicle Inductive Mesenchyme (5R01AR071047-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980791. Licensed CC0.

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