# Regulation of cell polarity by Wnt signaling

> **NIH NIH R35** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $468,539

## Abstract

This proposal concerns signaling mechanisms regulating cell orientation in the epithelial
plane in the vertebrate embryo that is known as planar cell polarity (PCP). This common
phenomenon is mediated by a group of conserved proteins that polarize to one side of
an epithelial cell in the tissue. Secreted Wnt proteins have been implicated in the control
of PCP, but whether and how Wnt proteins provide the directional input to the PCP
system remains unclear. Our laboratory has a long-term interest in Wnt signaling and
cell polarity, but mechanistic studies were hampered by lack of tractable models and
suitable molecular markers. Recently, our group has developed specific antibodies and
fluorescent sensors for PCP analysis and discovered a unique polarity of cells in
Xenopus gastrula epidermis and the neural plate. The proposed studies will use the new
tools to address the following key questions that continue to challenge the field. A. What
mechanisms are responsible for core PCP protein segregation in polarized cells? B.
What are the spatial cues or signals that control PCP? C. How does cell polarization
translate into morphogenetic cell behaviors? Our experiments will uncover molecular
mechanisms regulating polarization of the core PCP protein Vangl2 to the anterior apical
edge of cells in the Xenopus. Other studies will clarify the role of Wnt ligands in this
process and identify new proteins that function in PCP using mass spectrometry-based
approaches. These experiments will use Xenopus embryos, a unique in vivo model, in
which biochemical, embryological and cell biological approaches can be combined. The
proposed studies will advance the knowledge of basic cell biological mechanisms
underlying vertebrate early morphogenetic events, such as gastrulation and neurulation.
Since misregulation of Wnt and PCP signaling has been causally linked to many
congenital defects and syndromes, polycystic kidney disease and multiple cancers,
these studies are highly relevant to human health.

## Key facts

- **NIH application ID:** 9974552
- **Project number:** 5R35GM122492-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Sergei Sokol
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $468,539
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974552

## Citation

> US National Institutes of Health, RePORTER application 9974552, Regulation of cell polarity by Wnt signaling (5R35GM122492-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974552. Licensed CC0.

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