# Role of Etv4 and Etv5 in the self-renewal and differentiation of nephron progenitors

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $431,692

## Abstract

Abstract:
Etv4 and Etv5 (Etv4/5) are two transcription factors expressed in the developing mouse kidney, specifically in
the ureteric bud tips, the metanephric mesenchyme and the renal vesicle.
Our preliminary data using a mouse model of Etv4/5 deletion in the nephron progenitor cells (NPCs) and their
progeny demonstrate a critical role for these transcription factors during nephrogenesis; absence of Etv4/5
cause premature NPC exhaustion, thinning nephrogenic zone and hypoplastic/cystic kidneys at birth. In
addition, these mutants present segmentation defects as early as the s-shape body stage. We have generated
RNAseq data from NPC mutant and littermate control embryonic kidneys and identified Wnt4 as a downstream
target of Etv4/5.
Based on these preliminary data we hypothesize that Etv4/5 modulate nephrogenesis, at least in part, by
downregulating Wnt signaling in the NPCs and in the developing nephron. We further hypothesize that this
downregulation is required to favor both self-renewal of NPCs and differentiation of the early nephron.
We will test these hypotheses in two aims. In aim one we will investigate the crosstalk between Fgfs, Etv4/5
and Wnt4 signaling to promote self-renewal/prevent differentiation of the NPCs. In aim two we will investigate
how Etv4/5 and Wnt4 signaling affect nephron differentiation. These studies will provide further insight into the
signaling network driving progenitor self-renewal and differentiation; they will also expand our knowledge of the
cellular readout of Etv4 and Etv5 expression, therefore having a significant impact not only on the field of
developmental biology but also in cancer and in vitro organogenesis.

## Key facts

- **NIH application ID:** 10839391
- **Project number:** 5R01DK132052-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Cristina Cebrian Ligero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $431,692
- **Award type:** 5
- **Project period:** 2023-05-09 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839391

## Citation

> US National Institutes of Health, RePORTER application 10839391, Role of Etv4 and Etv5 in the self-renewal and differentiation of nephron progenitors (5R01DK132052-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10839391. Licensed CC0.

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