# Protocadherins in zebrafish visual system development

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $385,000

## Abstract

ABSTRACT
 The neural circuits underlying perception and behavior are assembled during development through
intricate and coordinated processes that include neurogenesis and migration, axon and dendrite extension and
arborization and synapse formation. In turn, conserved genetic programs orchestrate these dynamic
developmental processes. While much progress has been made in identifying genes that are important for
neural function, the mechanisms linking the action of gene products to the assembly of neural architecture and
to function are poorly understood. To address this important question, we have generated zebrafish mutants
and transgenic lines for several δ-pcdhs, evolutionarily conserved homophilic cell adhesion molecules that are
strongly expressed in the developing nervous system. We show that δ-pcdhs are expressed within radial
columns of neurons in the developing zebrafish optic tectum, and that the neurons within these columns are
siblings derived from one or a small number of progenitors. Loss of pcdh19 degrades the columnar
organization of pcdh19-expressing neurons, indicating that protocadherin function is required for column
maintenance. Moreover, pcdh19 mutants exhibit defects in visually guided behaviors. This proposal tests the
hypothesis that the shared inheritance of a δ-pcdh confers an identity to a column of neurons, and that
differential expression δ-pcdhs defines a code for organizing tectal circuitry and is essential for neural function
and behavior. Specifically, we will map the 3D distribution of neurons expressing individual δ-pcdhs, use in
vivo timelapse to determine the cellular roles of δ-pcdhs during column formation, and use in vivo calcium
imaging to determine the effects of δ-pcdh loss on the development of neural activity patterns. This study will
shed light on a fundamental aspect of neural organization and generate essential new insights into the
relationships between genes, the development of neural architecture and the origins of a range of
neurodevelopmental disorders attributed to members of the protocadherin subfamily of cell adhesion
molecules.

## Key facts

- **NIH application ID:** 10003250
- **Project number:** 5R01EY027003-05
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** JAMES DAVID JONTES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003250

## Citation

> US National Institutes of Health, RePORTER application 10003250, Protocadherins in zebrafish visual system development (5R01EY027003-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003250. Licensed CC0.

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