# Trophic interactions directing proper kidney development

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $336,138

## Abstract

Abstract
Renal function is dependent on an organized vascular network which coordinates with renal nerves to maintain
mammalian homeostasis. Despite their physiological significance, our understanding of how these networks
are established and influence kidney development are extremely limited. Our long-term goal is to dissect
neurovascular network formation and function during kidney development and apply these principles to
understanding and treating kidney disease. We hypothesize that patterned neurovascular networks modulate
kidney development through the localized release of signaling molecules. We rationalize that disruptions to
normal neurovascular form and function will have implications for kidney development and physiology. This is
significant to conditions such as congenital anomalies and neonatal acute kidney injury which could perturbate
developing neurovascular networks and contribute to disease progression. To this end, we have pioneered
efforts to interrogate the role of neurovascular networks in the developing mouse kidney. We have found that
ablating nerves and disrupting the patterning of neurovascular networks results in hypoplastic kidneys with
abnormal development. We predict that neurovascular cells release signaling factors that regulate kidney
development and have identified candidate factors. Our proposal aims to: 1) determine how nerves mediate
kidney development; 2) interrogate the role of neurovascular patterning in kidney development and implications
for function; 3) investigate how neurovascular produced signals promote kidney development. We will utilize a
combination of genetic mouse and human kidney organoid models, state-of-the-art imaging techniques,
quantitative analyses, and various modern and novel methodologies to carry out our investigations and gain
mechanistic insights. Adult renal physiology will be analyzed to understand how developmental phenotypes
correlate and lead to compromised function. Together, our findings will provide novel insights and advance our
understanding of the coordinated cellular functions required to establish a proper, functional kidney. Current
treatment options for patients with advanced kidney disease are limited to dialysis and transplant. Clearly, new
therapeutic strategies are necessary. Being able to engineer transplantable kidneys ex vivo or
regenerate/repair them in vivo would help alleviate the need for dialysis and donor organs which are in short
supply. However, to accomplish such feats requires a thorough understanding of how kidneys are formed
during development, and the cellular interactions which drive this process which includes neurovascular
networks.

## Key facts

- **NIH application ID:** 10312135
- **Project number:** 5R01DK121014-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lori L O'Brien
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,138
- **Award type:** 5
- **Project period:** 2020-02-21 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312135

## Citation

> US National Institutes of Health, RePORTER application 10312135, Trophic interactions directing proper kidney development (5R01DK121014-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312135. Licensed CC0.

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