# Functions of secreted Wnt inhibitors in hair follicle patterning and regenerative activity

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $46,593

## Abstract

PROJECT SUMMARY
Different regions of skin exhibit distinct properties and functions, including their patterns of hair follicle
distribution and regenerative properties. Hair loss diseases often have regional effects due to this variation in
skin biology. An extremely common example in both men and women is androgenetic alopecia, or AGA, also
known as male pattern baldness and female pattern hair loss. AGA affects only scalp hair, and is characterized
by disruption of signaling in and around the hair follicle (HF) that leads to inhibition of the hair growth cycle and
hair follicle miniaturization. Hair loss diseases can have negative psychological, social, and financial impacts.
Current treatments are only partially effective, and the molecular basis for regional variation in skin and hair
growth is not well-characterized. Delineating the mechanisms underlying skin and hair heterogeneity has the
potential to identify improved therapeutic approaches to hair loss and skin diseases. Wnt/β-catenin signaling is
crucial for the initiation, development, and regeneration of hair, and can be modulated by endogenous secreted
Wnt inhibitors. Dkk2 and Sostdc1 are secreted Wnt inhibitors that have regionally distinct expression patterns,
with relatively higher expression levels in regions of embryonic mouse skin that develop poorly regenerative
hair follicles or remain completely hairless. Preliminary data show that Dkk2 and Sostdc1 are also upregulated
in the dermal papilla of postnatal HFs as the anagen growth phase ends. The proposed research will test the
global hypothesis that Dkk2 and Sostdc1 dictate whether skin will be hair-bearing, determine HF size and
regenerative capacity, and control adult HF cycling. Aim 1 will delineate the roles of Dkk2 and Sostdc1 in HF
patterning during embryogenesis using Dkk2/Sostdc1 global null mice. Aim 2 will determine the postnatal
functions of these inhibitors in regulating HF size and cycling independent of their embryonic roles by inducing
deletion postnatally in Dkk2/Sostdc1 floxed mice. Successful completion of the proposed aims has the
potential to identify novel therapeutic targets for hair loss diseases and will provide the candidate with rigorous
training in experimental techniques and science communication that is essential for an independent research
career. Supplemented with the proposed mentorship experiences and collaborative intellectual environment,
this fellowship will accelerate the career progress of a promising PhD Candidate who is strongly committed to
skin development and regeneration research.

## Key facts

- **NIH application ID:** 10465941
- **Project number:** 1F31AR081127-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Alicia Ho
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,593
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465941

## Citation

> US National Institutes of Health, RePORTER application 10465941, Functions of secreted Wnt inhibitors in hair follicle patterning and regenerative activity (1F31AR081127-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465941. Licensed CC0.

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