# Protocadherin control of cell proliferation and differentiation

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $348,728

## Abstract

ABSTRACT
 During development, the division of progenitor cells is tightly regulated in time and place to produce the
appropriate number and types of cells; misregulation of proliferation or differentiation can lead to
morphogenetic defects and a variety of developmental disorders. The δ-pcdhs are a family of homophilic cell
adhesion molecules that have been linked to neurodevelopmental disorders, including autism and epilepsy.
They have additionally been identified as tumor suppressor genes in an array of cancers. Our preliminary data
reveal that mutant zebrafish lacking individual δ1-pcdhs (pcdh1a, pcdh7a or pcdh9) or δ2-pcdhs (pcdh17,
pcdh18b or pcdh19) all display increased cell proliferation in the early neural tube, resulting in excess neurons
later in development. In a preliminary study using in vivo timelapse, we show by direct observation that the
spatiotemporal dynamics of cell divisions is altered in the mutants. We further provide evidence that the δ-
pcdhs are regulators of the canonical Wnt signaling pathway and that both canonical Wnt signaling and the
Wnt receptor Ryk are required for the increased proliferation in δ-pcdh mutants. This proposal will test the
hypotheses that: 1) cell-cell interactions, mediated by δ-pcdhs, coordinate cell proliferation and neural
progenitor cell dynamics in the neuroepithelium; and 2) δ-pcdhs influence cell proliferation by regulating
canonical Wnt/β-catenin signaling through Ryk. These experiments will elucidate the mechanics of
fundamental events in nervous system development and provide important insights both into the underlying
causes of neurodevelopmental disease and to the role of δ-pcdhs in cancer.

## Key facts

- **NIH application ID:** 10390347
- **Project number:** 5R01GM141280-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** JAMES DAVID JONTES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $348,728
- **Award type:** 5
- **Project period:** 2021-04-10 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390347

## Citation

> US National Institutes of Health, RePORTER application 10390347, Protocadherin control of cell proliferation and differentiation (5R01GM141280-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10390347. Licensed CC0.

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