# Elucidating the regulation and function of FoxL1+ cell-derived Wnt5a during intestinal development

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2021 · $6,428

## Abstract

Project Summary
The objective of this proposal is to investigate the role of FoxL1+ telocytes during intestinal development through
its production of Wnt5a. Wnt5a is a non-canonical Wnt ligand that is essential for development of many organs,
including the intestine. The role of Wnt5a in early intestinal development has been examined in Wnt5a-/- mice,
which exhibit shortened intestines due to impaired apical basal polarity (ABP) during midgut elongation. However,
little is known about how Wnt5a expression is regulated, or its functions during postnatal development. Recently,
our lab showed a rare population of mesenchymal cells, the Foxl1+ subepithelial telocytes (FoxL1+ telocytes), to
be the essential source of canonical Wnt signals in the stem cell compartment. Furthermore, these FoxL1+
telocytes were found to express Wnt5a along the crypt wall and crypt-distal regions in adult mice. Therefore, I
generated FoxL1-Cre; Wnt5af/f mice and FoxL1-CreERT2; Wnt5af/f mice to elucidate expression regulation and
function of Wnt5a in FoxL1+ telocytes. This is an innovative approach because all previous Wnt5a studies lacked
knowledge of the distinct cell population expressing this gene, which limited the depth of functional studies that
could be performed. My model is the first to delete Wnt5a in a cell type-specific manner in the intestine, for an in
vivo assessment of Wnt5a function in its biological context. Aim 1 will determine whether FoxL1 regulates Wnt5a
expression to establish ABP during intestinal development. Using FoxL1-Cre; Wnt5af/f mice, I will assess ABP
integrity during midgut elongation, and perform western blotting and pulldown assays to elucidate the
mechanisms involved. Using FoxL1-/- mice, I will test the hypothesis that FoxL1 binds at the Wnt5a promoter and
is a direct regulator of Wnt5a expression by qRT-PCR, ChIP-seq, and luciferase assays. Aim 2 will use a
conditional Wnt5a knockout mouse model, FoxL1-CreERT2; Wnt5af/f, to investigate the role of Wnt5a in neonatal
crypt formation, a process that has never been characterized previously. I will use histological methods to see if
Wnt5a from FoxL1+ telocytes are required for this process. I will also perform immunohistochemical analyses,
western blotting, and qRT-PCR to determine whether Wnt5a antagonizes canonical Wnt/b-catenin signaling
during crypt formation. Finally, I will utilize a 3D organoid culture system for an ex vivo analysis of fetal crypt
development. Together, these Aims will elucidate the roles of FoxL1 and Wnt5a signaling in regulating
mammalian intestinal development, which may point to novel therapeutic targets for intestinal developmental
diseases and inflammatory diseases.

## Key facts

- **NIH application ID:** 10326366
- **Project number:** 5F31DK125008-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ayano Kondo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $6,428
- **Award type:** 5
- **Project period:** 2020-09-01 → 2021-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326366

## Citation

> US National Institutes of Health, RePORTER application 10326366, Elucidating the regulation and function of FoxL1+ cell-derived Wnt5a during intestinal development (5F31DK125008-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10326366. Licensed CC0.

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