# Retinoic acid gene regulatory networks in the mammalian kidney

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $403,637

## Abstract

Project Summary/Abstract
 Proper nephron endowment and segmentation are essential for building healthy kidneys. Nephron number
is highly variable among humans. Low nephron number is associated with increased risk of hypertension and
end-stage renal disease. A better understanding of the mechanisms of nephrogenesis will help us devise a
way to increase nephron endowment. Along the proximal-distal axis, the renal corpuscle is connected to the
collecting duct via the proximal tubule, loop of Henle, and distal tubule. Each nephron segment carries out
distinct physiological functions. Understanding how multipotent nephron progenitors make their cell fate
decisions to develop into different nephron segments is essential not only for building a functional nephron in
vitro but also for promoting regeneration after kidney injury. In this proposed study, we will investigate how
retinoic acid signaling regulates nephron endowment and segmentation. We found that, in mice, inhibition of
retinoic acid signaling in mesenchymal nephron progenitor cells caused significantly lower nephron
endowment. We also found that inhibition of retinoic acid signaling in the newly formed developing nephron
interfered with the formation and maturation of proximal tubule cells. Our preliminary data suggest that retinoic
acid signaling plays important roles in early and later stages of nephrogenesis, contributing to proper nephron
endowment and segmentation. In Aim 1, by manipulating retinoic acid signaling genetically in vivo and
pharmacologically in vitro, we will test if retinoic acid signaling is required for mesenchymal-to-epithelial
transition of nephron progenitors by coordinating with Wnt/-catenin signaling. To understand how retinoic acid
signaling contributes to nephron endowment, we will determine the retinoic acid gene regulatory network in
nephron progenitors. In Aim 2, by performing genetic gain-of-function and loss-of-function studies of retinoic
acid signaling in the newly formed developing nephron, we will test if retinoic acid signaling is necessary or
sufficient for the formation and maturation of proximal tubules. We will also determine the retinoic acid gene
regulatory network in the developing nephrons to understand how retinoic acid signaling regulates nephron
segmentation. Our proposed studies will fill a longstanding gap of knowledge in the molecular mechanisms
underlying the determination of nephron endowment as well as the formation or maturation of proximal tubules
in mammals. Our long-term goals are to devise a way to increase nephron endowment during development
and to generate nephron tubule cells for potential cell replacement therapy.

## Key facts

- **NIH application ID:** 10102130
- **Project number:** 5R01DK120847-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Joo-Seop Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,637
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102130

## Citation

> US National Institutes of Health, RePORTER application 10102130, Retinoic acid gene regulatory networks in the mammalian kidney (5R01DK120847-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102130. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*