# MOLECULAR MECHANISMS OF RETINAL CIRCUIT ASSEMBLY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

The morphology of axons and dendrites shapes the connectivity and function of neuronal circuits; and
dysmorphic axons and dendrites are a common feature of neurodevelopmental disorders. To establish cell-type-specific morphologies, developing neurites need to (1) grow towards and branch in the right places (i.e. neurite
targeting), (2) elaborate arbors with distinct branching patterns and geometries (i.e. neurite shape), and (3)
occupy appropriate territories (i.e. neurite size). How axons and dendrites grow to an exact size, how arbor size
regulates connectivity, and how it influences specific circuit computations is not well understood. In preliminary
studies, we identified four cell adhesion molecules (CAMs; Amigo1, Amigo2, netrin-G1, and NGL1) that regulate
dendrite and axon size of neurons in two circuits of the retina: the direction selective (DS) circuit, which extracts
motion information in the inner retina, and the rod bipolar pathway, which transmits dim-light-signals from the
outer to the inner retina. Starburst cells have radially symmetric arbors that overlap extensively among neighbors
and express Amigo2. The central two thirds of each arbor receive input and the peripheral third provides output.
Inhibitory input from starburst cells is critical for DS responses of ganglion cells. Neurite size of starburst cells is
increased in Amigo2 knockout (Amigo2-/-) mice, while functional compartmentalization is maintained. In Aim 1,
we will analyze the molecular mechanisms of Amigo2’s actions, test its influence on neurite morphology and
connectivity, DS circuit function, and image stabilizing head and eye movements. At the first stage of the rod
bipolar pathway, horizontal cell axons mediate lateral inhibition among rods, which provide input to rod bipolar
dendrites. Horizontal cells express Amigo1. In Amigo1-/- mice, horizontal cell axons and rod bipolar dendrites are
both reduced in size. In Aim 2, we will characterize the signaling mechanism of Amigo1, explore territory
matching between synaptic partners, analyze effects on connectivity and measure light sensitivity along the rod
bipolar pathway, and in behavioral responses. At the second stage of the rod bipolar pathway, netrin-G1-expressing rod bipolar axons synapse onto NGL1-expressing AII cells. Rod bipolar axon size is reduced in netrin-
G1-/- and NGL1-/- mice, suggesting that retrograde signals of trans-synaptic netrin-G1/NGL1 complexes regulates
axon growth. In Aim 3, we will explore whether forward signals control AII arbor size. We will determine how
netrin-G1/NGL1 complexes affect the number, ultrastructure and function of synapses between rod bipolar and
AII cells, and assess their influences on light responses along the rod bipolar pathway and on the ability of mice
to detect dim light flashes. Together these studies will provide insights into the molecular mechanisms that control
axon and dendrite size in the retina, reveal how neurite size regulates connectivity, and how it ...

## Key facts

- **NIH application ID:** 9894802
- **Project number:** 5R01EY027411-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Daniel Kerschensteiner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894802

## Citation

> US National Institutes of Health, RePORTER application 9894802, MOLECULAR MECHANISMS OF RETINAL CIRCUIT ASSEMBLY (5R01EY027411-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894802. Licensed CC0.

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