# Primary cilia as regulators of vascular stability during embryonic development

> **NIH NIH K99** · WASHINGTON UNIVERSITY · 2024 · $108,405

## Abstract

PROJECT SUMMARY/ABSTRACT
The process of vascular stabilization—which includes mural cell recruitment to the blood vessels—is critical for
organism development and survival. The hemodynamic forces from blood flow itself play a part in these
stabilization events; however, there are still many gaps in our understanding of how this mechanosensitive
signaling occurs and how blood vessel integrity is influenced by disruptions in mechanosensing. Primary cilia on
endothelial cells (ECs) have been proposed to be mechanosensitive structures that facilitate signaling in
response to hemodynamic forces, though most of our current understanding of this process stems from in vitro
work. Interestingly, genetic studies from patient cohorts with congenital heart defects (CHD) reveal an
unexpectedly high association with cilia-related gene variants. Consequently, the study of hemodynamics,
primary cilia, and congenital cardiovascular defects is a largely unexplored field that could have a meaningful
impact on understanding and treating CHD. Thus, the objectives of this proposal are to determine if EC cilia
respond to changes in hemodynamic forces during development, to define a mechanism for primary cilia in
vessel stabilization, and to model novel cilia-related human CHD variants and assess the vascular phenotypes
using the zebrafish animal model. The proposed studies are based on robust preliminary data showing EC
primary cilia are evident—and unexpectedly, abluminal—during axial vasculature stabilization events, and that
embryos with mutant cilia display phenotypic abnormalities associated with compromised vascular stability.
Additional preliminary data suggests that both luminal and abluminal cilia can assemble or disassemble in
response to changes in blood flow. Furthermore, embryos with mutant cilia display aberrant mural cell
association. Together these data support the central hypothesis that endothelial primary cilia are
mechanosensitive regulators of cardiovascular development in part due to their influence on mural cell function
and vascular stability. My hypothesis will be tested with the three aims: 1) assess the orientation and localization
of EC cilia in response to hemodynamic changes across vascular development, 2) determine the role of primary
cilia in mural cell recruitment, differentiation, and vascular stabilization during development, and 3) utilize human
CHD data to identify cilia-related defects and analyze the functional consequences of those gene mutations in
zebrafish. This work is innovative because it will utilize the zebrafish model to explore mechanosensitive
mechanisms linked to vascular stabilization events in vivo. The proposed research is significant in its aim to
provide novel insight to the EC cilia field by identifying abluminal cilia and demonstrating that they are
mechanosensitive structures in vivo, in addition to clarifying the impact of primary cilia on vascular stabilization
and congenital cardiovascular defects.

## Key facts

- **NIH application ID:** 10985570
- **Project number:** 1K99HL171944-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sarah Ann Wilson-Colijn
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,405
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985570

## Citation

> US National Institutes of Health, RePORTER application 10985570, Primary cilia as regulators of vascular stability during embryonic development (1K99HL171944-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985570. Licensed CC0.

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