# Deciphering the molecular mechanisms in photoreceptor wiring

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $400,000

## Abstract

Project Summary
Proper transmission of visual information relies on photoreceptors forming appropriate synaptic connections
during development. Nearly all retinal diseases that lead to blindness are caused by loss of photoreceptors
connections. Thus, elucidating the molecular mechanisms that mediate proper photoreceptor connectivity may
lead to better therapies to treat patients with retinal diseases. During development, photoreceptors first synapse
selectively to horizontal cells, where the dendrites of horizontal cells synapse to cone photoreceptors and the
axon connects to rod photoreceptors. Cones and rods then synapse to their respective bipolar target. Cones
synapse to cone bipolars and rods to rod bipolars. The molecular mechanisms that guide selective wiring of the
different photoreceptors to their distinct synaptic partners remains poorly understood. Our data shows the L1 cell
adhesion molecule Neurofascin (Nfasc) is localized to the synaptic layer during development and expressed in
rods, horizontal cells, and rod bipolars. Moreover, we find disruption of Nfasc results in rod synaptic defects and
abnormal rod-driven visual responses. As Nfasc is known to mediate adhesive interactions between neurons,
we propose Nfasc is a key molecule mediating selective connectivity of rods to horizontal cells and then to rod
bipolars. In addition, we find other cell adhesion molecules that are known to work alongside Nfasc (i.e. Caspr,
Cntn1, Nrcam), to be expressed in the complementary cone pathway. Thereby, we hypothesize that restricted
expression of cell adhesion molecules mediates selective wiring of the different photoreceptors to their respective
targets. To test our hypothesis, we will mouse transgenics, in vivo genetic manipulations, and single neuron
labeling approaches to identify the key molecular interactions that guide photoreceptors to synapse selectively
to different partners. The proposed research will elucidate the adhesive molecular interactions that instruct
selective wiring of photoreceptors to horizontal cells (Aim 1) and to bipolar neurons (Aim 2). Through these
experiments, we will uncover the molecular mechanisms involved in complex wiring of neural circuits during
development. This knowledge will be necessary to develop new strategies to restore vision in those with retinal
diseases.

## Key facts

- **NIH application ID:** 10280111
- **Project number:** 1R01EY033037-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Elizabeth Zuniga-Sanchez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280111

## Citation

> US National Institutes of Health, RePORTER application 10280111, Deciphering the molecular mechanisms in photoreceptor wiring (1R01EY033037-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10280111. Licensed CC0.

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