# Formation and Function of the Meninges

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2022 · $77,750

## Abstract

Project summary
 The meninges encase the CNS from its earliest stages of development and persist as a protective
covering for the adult CNS. Many studies show the meninges, in particular the meningeal fibroblasts, has vital
roles in controlling developmental neurogenesis and neuronal migration and congenital defects in human
brain development can arise from meningeal defects. The meninges also contain unique immune and
vascular cell populations (blood and lymphatics) that are now known to serve key functions in neuro-immune
surveillance, cerebrospinal fluid drainage and CNS waste removal, thus supporting overall CNS health and
function. Despite this, we have an incomplete understanding of the cellular and molecular mechanisms that
control formation of the meninges. We know very little about the development of the different fibroblast
populations that produce factors that help control brain development and may have roles in development of
other meninges cell types (immune cells) and adjacent structures like the calvarium. Our prior work
demonstrates that meningeal fibroblast populations of the pia, arachnoid and dura layers around the forebrain
are transcriptionally unique and begin to express layer specific markers at early stages of brain development.
We and others have previously shown that the transcription factor Foxc1 is key for this meningeal layer
specification. Here we propose to use a new, meninges conditional Foxc1 mouse mutant in combination with
single cell transcriptomics (scRNAseq) to begin to identify: 1) the normal developmental progression of
meningeal fibroblast layer populations and identify signaling pathways that underlie the failed development in
Foxc1 mutants and 2) identify signals produced by prenatal meningeal fibroblasts that control maturation of
other meningeal populations, in particular immune cells, and the adjacent calvarium. Completion of
experiments outlined here will serve as foundational pilot data for future grant applications, support our long-
term research goals in studying meninges control of CNS development and function and will be an important
resource for researchers studying meninges-related structure, process, disease or malformation.

## Key facts

- **NIH application ID:** 10435092
- **Project number:** 1R03NS127154-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julie Siegenthaler
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,750
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435092

## Citation

> US National Institutes of Health, RePORTER application 10435092, Formation and Function of the Meninges (1R03NS127154-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10435092. Licensed CC0.

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