# Cell-cell communications in neural circuit assembly

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $434,334

## Abstract

PROJECT SUMMARY
A key question in neurobiology is how individual neurons precisely connect with each
other to form functional circuits during development. Understanding the mechanisms of
neural circuit assembly in the mammalian brain may provide insights into the etiology of
human brain disorders. In the mammalian brain, each neuron on average forms
connection with thousands of other neurons. The assembly of these complex circuits
depends on cell-cell communication during many steps of neural development.
In the previous three cycles of this grant, we have developed methods such as MADM
(Mosaic Analysis with Double Markers) and viral-genetic manipulations in mice that
allowed us to label and genetically manipulate specific neuron cell types, down to
individual neurons, and study genes that play key roles in dendrite morphogenesis and
target selection of axons. Specifically, we have recently identified two cell-surface
proteins, Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2), that are expressed in
complementary patterns in the interconnected nodes of hippocampal network, following
a “Ten3→Ten3, Lphn2→Lphn2” connectivity rule . We have shown that Lphn2 acts as a
heterophilic repulsive ligand and Ten3 acts as a homophilic attractive ligand to direct
Ten3+ proximal CA1 axons to selectively target to distal subiculum; at the same time,
Ten3 acts as a repulsive ligand to direct Lphn2+ axons to proximal subiculum. We have
also developed a method that allows us to profile cell-surface proteomes with exquisite
sensitivity and spatiotemporal control.
In this proposal, we will expand on both of these recent advances. Specifically, we will
investigate whether Ten3 and Lphn2 instruct wiring specificity in multiple nodes of the
extended hippocampal network and in other brain regions, how Ten3-Lphn2 interaction
leads to axon repulsion, and whether G protein signaling is essential for Lphn2’s action
as a receptor or a ligand. Complementary to the in-depth studies of Ten3 and Lphn2, we
will use our cell-surface proteomic profiling methods to broadly survey changes of cell-
surface proteomes from developing to mature neurons, and to identify new cell-surface
proteins that regulate dendrite morphogenesis and neural circuit assembly.

## Key facts

- **NIH application ID:** 10763377
- **Project number:** 5R01NS050835-17
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** LIQUN LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,334
- **Award type:** 5
- **Project period:** 2005-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763377

## Citation

> US National Institutes of Health, RePORTER application 10763377, Cell-cell communications in neural circuit assembly (5R01NS050835-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10763377. Licensed CC0.

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