# Development of neuronal circuits for innate behavior

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $349,167

## Abstract

Proper motor circuit formation is necessary for all behavior. However, motor circuit development is poorly
understood. My lab is taking a first principles approach to this problem. We are building a bridge between
neuron birth from stem cells to mature motor circuit architecture. The Drosophila larval nerve cord is an ideal
and uniquely-suited system for these studies because neuronal stem cell lineages and neuronal circuits are
map at single cell resolution. Furthermore, Drosophila has been used to generate many fundamental
discoveries relevant to neurogenesis in vertebrates, and recent work from my lab revealed remarkable
parallels between motor system development in flies and vertebrates. This demonstrates that comparison
between different species is essential for identifying fundamental principles underlying motor circuit
development. In Aim 1, we discriminate among attractive models of lineage-based motor circuit assembly. The
two objectives of this aim are to comprehensively determine lineage, birth time, and synaptic wiring of neurons
from a single lineage, NB3-3, as well as the synaptic partners of NB3-3 progeny, and to generate tools to study
assembly of circuits containing NB3-3 progeny in real time and in vivo. In Aim 2, we test the hypothesis that
Temporal Identity transcription factors (TFs) direct circuit assembly. Temporal Identity TFs cause stem cells to
generate different neurons over time. First, we describe new preliminary data in which we manipulate temporal
identity TF expression in a single lineage to produce a series of motor neurons with early-born molecular
identities at abnormally late times during development. Motor neurons born at the “wrong” time still form
synaptic partnerships with muscles that are characteristic of their molecular identity. These data provide
support for the hypothesis that lineage-intrinsic gene expression can control circuit assembly. However,
muscles are a stable physical substrate in comparison to neurons in the CNS during neurogenesis. The
objective of this aim is to examine the same manipulation in the context of neuron-neuron synapses in the
CNS. We use an innovative combination of sophisticated lineage tracing, neuronal stem cell specific gene
manipulation, calcium imaging, and electron microscope connectomic approaches. This includes use of
cutting-edge “comparative connectomics”, in which circuit wiring in two different genetic backgrounds can be
compared. These innovations allow us to study circuit assembly at single neuron resolution. Achieving single
neuron resolution is a significant advance, which is important because this is the level at which wiring decisions
are made. The experiments described here are significant because they will reveal fundamental principles of
lineage-based motor circuit development. This has wide ranging implications for the genetic basis of behavior,
neuro-developmental motor disease, and stem cell therapy for spinal cord injury. Thus, this grant proposal is...

## Key facts

- **NIH application ID:** 10460967
- **Project number:** 5R01NS105748-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ELIZABETH (Ellie) S HECKSCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $349,167
- **Award type:** 5
- **Project period:** 2018-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460967

## Citation

> US National Institutes of Health, RePORTER application 10460967, Development of neuronal circuits for innate behavior (5R01NS105748-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460967. Licensed CC0.

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