# Cell-cell communications in neural circuit assembly

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $375,758

## 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 two cycles of this grant, we have focused on developing MADM (Mosaic
Analysis with Double Markers) in mice. MADM labels with two distinct colors isolated
individual neurons or groups of neurons that share a common lineage. At the same time,
MADM can render neurons labeled with one of the colors homozygous mutant for a
gene of interest and neurons labeled with the second color wild type as internal controls.
MADM has allowed researchers to examine gene function in mammalian neural
development (as well as other processes) with single-cell resolution, and enabled many
new discoveries. In this renewal, we will utilize MADM and other tools we have
developed in the previous grant cycles to study cell-cell communications in neural circuit
assembly in the mouse brain. Specifically, we focus on two classes of proteins:
neurotrophin receptors and teneurins.
 Using MADM analysis of the neurotrophin receptor TrkC, we have previously shown
that sparse but not global knockout of TrkC in Purkinje cells reduces dendritic growth
and branching, suggesting a competitive mechanism for dendrite morphogenesis. We
will investigate the cellular mechanisms by which TrkC-mediated competitive dendrite
morphogenesis using in vivo imaging, test whether postsynaptic activity required for
Purkinje cell dendrite development, and the relationship between activity and TrkC
signaling. We will also explore the function of neurotrophin receptor TrkB in neuronal
morphogenesis. From our studies in Drosophila olfactory circuit assembly, we identified
two teneurins, which are evolutionally conserved type II transmembrane proteins, that
instruct synaptic partner matching via homophilic attraction. We will test whether
teneurins also mediate cell-cell interaction in neural circuit assembly in the mouse brain
using a combination of MADM analysis, conditional knockout, virus-mediated
misexpresssion, and in vitro assays.

## Key facts

- **NIH application ID:** 9912193
- **Project number:** 5R01NS050835-14
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** LIQUN LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,758
- **Award type:** 5
- **Project period:** 2005-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912193

## Citation

> US National Institutes of Health, RePORTER application 9912193, Cell-cell communications in neural circuit assembly (5R01NS050835-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9912193. Licensed CC0.

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