# Novel mechanisms of vasculogenesis

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $515,292

## Abstract

Project Summary
 Multiple vascular diseases including hypertension, diabetes, atherosclerosis, and others are associated
with the dysfunction of vascular endothelium. However, there are currently no effective methods to incorporate
new endothelial cells into damaged vessels in vivo which could contribute to vascular regeneration and repair.
 New blood vessels form by two distinct mechanisms, vasculogenesis, which is differentiation of
vascular endothelial cells de novo, and angiogenesis, formation of new vessels by branching from the existing
vessels. It is currently thought that vasculogenesis is largely limited to the initial vascular network during
embryogenesis, while the majority of the later vessels form by angiogenesis from the existing vasculature.
 While it is difficult to study vasculogenesis in the mammalian embryos, zebrafish has emerged as an
advantageous model system to study vascular development. Molecular mechanisms that control vascular
development are highly conserved between all vertebrates including zebrafish and humans.
 Here we have discovered a novel population of putative vascular progenitors in the zebrafish embryos.
These cells show high expression of ETS transcription factor etv2, a known key regulator of vasculogenesis,
and are located adjacent to the pronephros (pronephros-associated cells, PACs). Our preliminary data indicate
that PACs are the major source of organ specific vasculature, and they contribute to the embryonic vasculature
by a novel mechanism of cell intercalation into functional blood vessels. Our data further suggest that PACs
are likely conserved in mammalian embryos. In addition, we have identified Junctional Adhesion Molecule
Jam2b as one of key regulators required for PAC formation. We hypothesize that PACs are a novel group of
multipotent vascular progenitors which provide important contribution for vascular growth.
 The following specific aims are proposed: 1) Define contribution of PACs to different types of blood
vessels; 2) Identify functional role for PACs in vascular development; 3) Identify the role of Jam2b and other
upstream regulators in the formation of PACs and vascular development. Lineage tracing approaches will be
employed to determine contribution of PACs to different types of vessels in zebrafish embryos. PAC ablation
and etv2 conditional inhibition strategies will be used to test the functional role of PACs in zebrafish, and their
formation will also be investigated in murine embryos. The role of jam2b in PAC formation, its interaction with
Vegf signaling pathway, and functional roles of other PAC-enriched genes will be analyzed in zebrafish.
 Data obtained in this proposal will answer the key questions regarding the identity and functional role of
PACs, and are likely to uncover a novel mechanism of vascular growth. The mechanisms of vasculogenesis
are highly conserved, and our preliminary data suggest that similar progenitors are also present in the
mammalian embryos. Understan...

## Key facts

- **NIH application ID:** 10418662
- **Project number:** 5R01HL153005-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Saulius Sumanas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $515,292
- **Award type:** 5
- **Project period:** 2021-06-05 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418662

## Citation

> US National Institutes of Health, RePORTER application 10418662, Novel mechanisms of vasculogenesis (5R01HL153005-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10418662. Licensed CC0.

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