# Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2023 · $38,743

## Abstract

PROJECT SUMMARY
 Perivascular spaces (PVSs) are fluid-filled spaces surrounding vessels of the central nervous system,
are thought to have important roles in maintenance of brain health, and are a unique niche for a variety of
perivascular cell types. A cell type of particular interest is perivascular fibroblasts (PVFs) which are poorly
characterized, and their functions are largely unknown. PVFs are known to reside on the outside the vascular
smooth muscle layer of medium-to large-diameter vessels in the adult mouse central nervous system, and are
primarily identified by expression of Collagen-1 and Platelet-derived growth factor receptor (PDGFR)a and
PDGFRb. However, nearly nothing is known about the developmental origins, or the cellular and molecular
mechanisms important for PVF development. Preliminary data suggests PVFs emerge from a population of cells
in the meninges and gradually populate brain PVSs during postnatal development, but this has not yet been
investigated further. These gap in knowledge is a major barrier to developing novel tools to investigate the role
of PVFs in brain homeostasis and disease. The objective of this proposal is to investigate the developmental
origins, cellular dynamics, and molecular signaling mechanisms involved in PVF development. In Aim 1, I will
use a combination of transgenic mouse lines that label PVFs, optical tissue clearing, ex vivo imaging, and a
multi-color lineage tracing reporter to investigate the cellular origins and dynamics of developing PVFs. In Aim
2, I will use intracisternal cerebrospinal fluid tracer assays to determine the relationship between the timing of
PVF development and PVS function. Finally, in Aim 3 I will investigate PDGF signaling as a potential mechanism
controlling PVF development. Together, this project will be the first to fully characterize how PVF development
occurs and whether or not PDGF signaling is involved.

## Key facts

- **NIH application ID:** 10578680
- **Project number:** 5F31NS125875-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Hannah Elizabeth Jones
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $38,743
- **Award type:** 5
- **Project period:** 2021-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10578680

## Citation

> US National Institutes of Health, RePORTER application 10578680, Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling (5F31NS125875-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10578680. Licensed CC0.

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