# Retinoic Acid in Development of CNS Vasculature

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $334,572

## Abstract

Project Summary
 Central nervous system (CNS) vasculature, like the tissue is supplies, is truly unique. The distinctive
features of the CNS vasculature, including an unusually dense vascular plexus and barrier properties, are
stimulated during development by a mixture of bioactive ligands produced by the neural environment. In this
way, the CNS builds a vascular plexus to fit its needs. Despite recent advances, many neuro-vascular cues
likely remain unidentified and how endothelial cells integrate diverse neural-derived signals to ensure vascular
growth and integrity is not well understood. Addressing these gaps in our knowledge will provide insight into
the underlying causes of developmental neuro-vascular pathologies and potentially reveal novel therapeutic
strategies to correct these defects and prevent irreversible damage to the CNS. Further, greater insight into
basic mechanisms of neuro-vascular development could offer new tactics to target regenerative and
pathological angiogenesis in the mature CNS.
 We have identified a novel role for Retinoic Acid (RA) signaling in CNS vascular development. Based on
our analysis of endothelial RA signaling mutants, we hypothesize that RA ensures successful CNS vessel
growth, maturation and stabilization by modulating Wnt-β-catenin signaling. We will test this hypothesis in
three distinct aims. In Aim 1, we will 1) identify a role for RA signaling in controlling brain endothelial cell and
pericyte proliferation required for vascular stability and 2) determine how RA, via its receptor RARα, inhibits
Wnt-β-catenin activity in CNS endothelial cells. In Aim 2, we will determine how transcription factor Sox17,
regulated by endothelial RA and Wnt-β-catenin signaling, regulates CNS vascular growth and brain pericyte
recruitment. In Aim 3 we will elucidate the function of RA in retinal vascular development and identify a role for
RA deficiency in the developmental vascular pathology retinopathy-of-prematurity. Completion of experiments
in this proposal will provide new knowledge about molecular regulation of neurovascular development and will
add greatly to the working model of CNS endothelial-pericyte regulation, an important framework that can be
used to develop new hypothesis regarding how neurovascular pathologies develop and can ultimately be
treated.

## Key facts

- **NIH application ID:** 9951116
- **Project number:** 5R01NS098273-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julie Siegenthaler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,572
- **Award type:** 5
- **Project period:** 2016-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951116

## Citation

> US National Institutes of Health, RePORTER application 9951116, Retinoic Acid in Development of CNS Vasculature (5R01NS098273-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9951116. Licensed CC0.

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