# Mechanisms regulating Meningeal Development and Function

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $246,511

## Abstract

ABSTRACT/PROJECT SUMMARY
The meninges, a protective layer ensheathing the Central Nervous System (CNS), is a highly vascularized,
complex tissue that serves as the primary site for equilibration of cerebrospinal fluid (CSF). CSF, a
transparent, colorless fluid that recirculates throughout the CNS, supports brain buoyancy, prevents
vascular and neuronal collapse, and provides buffering against mechanical injury. Given the functional
importance of CSF for CNS homeostasis, the clearance of metabolic waste from this fluid compartment is
carried out as a nearly constant process. This waste removal process relies heavily on groups of vascular-
associated, perivascular cells within the meninges that filter the byproducts from the CSF and transport
them into circulation via the lymphatic system for ultimate disposal. Hence, the interaction between
meningeal cells and the vascular system is crucial to safeguard brain homeostasis. Some forms of
neurodegeneration have been linked with a decline in homeostasis and an increase in metabolic waste
accumulation in an age-, diet- or pathogenic infection-dependent manner. Understanding vascular-
associated meningeal cells make-up, developmental origin, genetic regulation and function is an important
long-term undertaking to fully grasp how neurodegeneration occurs in response to these conditions. The
amenability of the zebrafish for live imaging represents a remarkable advantage over other models to study
meningeal development in vivo. In Aim 1, I will use newly developed transgenic lines labeling pan-
meningeal and meningeal perivascular cell populations in vivo to uncover the developmental origin of these
cells using a combination of high resolution confocal imaging for lineage tracing studies, Transmission
Electron Microscopy to characterize their cellular structures, and single cell and “RiboTag” RNA-
sequencing to identify gene programs regulated in meningeal populations. Aim 2 will uncover the functions
that meningeal cells play in supporting CNS homeostasis and maintenance. Analysis will be done utilizing
readily available mutants that present defects in meningeal development. In addition, as an unbiased
approach, I will utilize a forward genetic mutagenesis screen to uncover genes required for proper
meningeal development and function. Lastly, complementary in vivo high resolution confocal imaging and
in vitro cell culture assays will be utilized to uncover biochemical changes in meningeal cells resulting from
age, diet, and infection in both wild type and mutant zebrafish populations (Aim 3). These aims are
designed to expand the current knowledge of meningeal cellular components, genetic signals controlling
their development, and a better understanding of their interaction with the vasculature. This proposal offers
a foundational niche in the vascular developmental biology field through which I can launch a future tenure-
track research faculty position.

## Key facts

- **NIH application ID:** 10866593
- **Project number:** 5R00HD098273-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Marina Venero Galanternik
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,511
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866593

## Citation

> US National Institutes of Health, RePORTER application 10866593, Mechanisms regulating Meningeal Development and Function (5R00HD098273-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10866593. Licensed CC0.

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