# Waking up the nervous system: Molecular characterization of neuronal leader cells and their role in brain development

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $75,110

## Abstract

Project Summary/Abstract
Learning how spontaneous neuronal activity shapes embryonic brain development is critical for understanding
neurodevelopmental processes, with implications in neurological or neuropsychiatric disorders. Early sporadic
activity is essential for the formation of mature correlated neuronal networks. To date, we have had success in
identifying the motor circuit as the first circuit to function in a developing zebrafish embryo. In addition, a few
neurons, the “leader cells”, are the first neurons to obtain spontaneous neuronal activity. This spontaneous
activity is followed by the formation of small synchronized neuronal networks that elaborate into complex circuits
as development progresses. However, due to their sparsity and transient nature, molecular characterization of
leader cells has been a challenge. This proposal aims to combine zebrafish genetics with powerful new methods
for single-cell transcriptomic profiling to deliver a high-resolution map of activity-dependent development and to
use it to identify activity-dependent gene programs in a cell-type specific manner and profile leader cells. The
proposal focuses on integrating new technologies into discovering how the embryonic vertebrate brain develops
in an activity-dependent manner. The aims are to perform comprehensive molecular profiling of the leader cells
as they acquire spontaneous activity in the developing vertebrate nervous system, identify potential genetic
regulators (Aim 1), and assess how perturbations to leader cell activity shape circuit maturation and brain
development (Aim 2). The proposed work leverages recent developments from several disciplines: single-cell
RNA sequencing (scRNA-seq), zebrafish genetics, and optogenetics. Specifically assessing how the brain
develops during health and when the motor circuit, the first circuit to function in the zebrafish nervous system, is
disrupted. The ideal setting to carry out this proposal is with the co-mentoring of Dr. Wagner, who developed
TRACERSEQ and STITCH to map the quantitative relationship between cell states and lineages in healthy and
perturbed contexts using quantitative biology techniques and Dr. Kriegstein, an expert in development,
genomics, and stem cell biology. Overall, these studies will lead to general insights into how transcriptional
profiles of neuronal and non-neuronal cells coordinate to create a healthy brain with proper cell proliferation and
differentiation in an activity-dependent manner.

## Key facts

- **NIH application ID:** 10315708
- **Project number:** 1F32MH127777-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nicole Ann Aponte-Santiago
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,110
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315708

## Citation

> US National Institutes of Health, RePORTER application 10315708, Waking up the nervous system: Molecular characterization of neuronal leader cells and their role in brain development (1F32MH127777-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10315708. Licensed CC0.

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