# Investigating the role of the blood-brain barrier in trafficking prenatal liver-derived immune cells into the brain

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $41,632

## Abstract

PROJECT SUMMARY
The blood-brain barrier (BBB) plays a crucial role in brain health, but its role in brain development and the
cellular interactions which govern its formation remain unknown. Recent studies have revealed specific time
points during which microglia-like progenitors exit the prenatal liver and migrate into the brain, suggesting a
complex development and function of the BBB throughout gestation. Furthermore, once in the brain, these
progenitors differentiate into a population of cells similar to microglia, which are traditionally thought to arise
from progenitors that exit the yolk sac and migrate directly into the brain. Understanding the developmental
changes in BBB permeability is essential to unraveling the mechanisms by which it regulates cellular trafficking
into the brain. Dr. MacKenzie's lab published these findings and is currently investigating the migration of these
prenatal liver-derived (PL-derived) immune cells into the brain using an innovative in utero prenatal liver
injection model. Additionally, Dr. Crouch's lab has developed a novel strategy to isolate endothelial and mural
cells, key vascular cell types of the developing brain vasculature, for in vitro study and single-cell RNA
sequencing analysis. With these techniques, this proposal aims to elucidate the cellular and molecular
development of the BBB and its impact on cellular trafficking into the brain. Our overall hypothesis is that
immature venous-like vasculature mediates the entry of PL-derived immune cells into the brain due to its
heightened BBB permeability during development. To address this hypothesis, we will first characterize the
spatiotemporal development of the BBB, identifying cell types and anatomical regions associated with
increased vascular permeability. Second, we will trace the entry of PL-derived immune cells into the brain and
track changes in their cell identity over time. The outcomes of this research will advance our understanding of
brain vascular development and potentially inform the development of therapeutics targeting the unique
selective permeability of the prenatal brain vasculature.

## Key facts

- **NIH application ID:** 10901479
- **Project number:** 1F31NS137776-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Kaylee Wedderburn-Pugh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,632
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901479

## Citation

> US National Institutes of Health, RePORTER application 10901479, Investigating the role of the blood-brain barrier in trafficking prenatal liver-derived immune cells into the brain (1F31NS137776-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10901479. Licensed CC0.

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