# Linking neuronal identity transcription factors to neural circuit establishment and maintenance

> **NIH NIH F32** · UNIVERSITY OF OREGON · 2022 · $69,802

## Abstract

PROJECT SUMMARY/ABSTRACT
Neuronal identity is generated during development, with identity characterized by neuron-specific
gene expression, axon/dendrite morphology, and connectivity. Homeodomain transcription factors
(TFs) are required for establishing gene expression and neuronal morphology, but whether they are
required for neuronal connectivity is unknown. Understanding the developmental processes
generating neuronal identity in general, and connectivity in particular, is essential for understanding
brain assembly and function. An attractive model is that homeodomain TFs – known to regulate
neuronal molecular and morphological identity – also facilitate the expression of cell surface
molecules that allow the formation of highly-specific neural connections. Connections between
individual neurons contribute to neural circuits, which allow sensation, movement and cognition.
Proper circuit function throughout life relies on continued circuit remodeling, both synaptically and
structurally. Interestingly, homeodomain TFs are expressed in adult neurons, well after neuronal
identity has been established. I hypothesize that the homeodomain TFs are required for neural
circuit establishment and maintenance throughout life. To test this, I have performed a
systematic screen for homeodomain TFs required for the function of a locomotor neural circuit in
Drosophila, the Moonwalker Descending Neuron (MDN) and Pair1 circuit. I have identified 16
homeodomain TFs required for MDN or Pair1 optogenetic induced locomotion. In Aim 1, I will test
how these 16 homeodomain TFs contribute to neuronal identity by assaying molecular identity,
axon/dendrite morphology, and connectivity. My pilot experiments have already shown that the
homeodomain TF Bicoid is required for connectivity but not molecular identity or morphology. In Aim
2, I will utilize how the MDN-Pair1 circuit is remodeled during Drosophila metamorphosis and persists
in the adult fly. I will assay whether the TFs required for establishing MDN-Pair1 connectivity are also
required for maintaining the MDN-Pair1 circuit throughout adulthood. My pilot data shows that Bicoid
is also expressed in the adult Pair1 neurons. My overarching goal is to advance the understanding of
how developmental mechanisms, specifically homeodomain TFs, establish circuits during
development and maintain circuits after periods of plasticity/remodeling. Given that fly and
mammalian neurogenesis share many conserved features, that homeodomain TFs are highly
conserved between species, and that aberrant neural circuits have been implicated in
neurodevelopmental and psychiatric disorders, we expect our results to be both translatable and
therapeutically relevant.

## Key facts

- **NIH application ID:** 10386149
- **Project number:** 1F32HD105344-01A1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Kristen M Lee
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 1
- **Project period:** 2022-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386149

## Citation

> US National Institutes of Health, RePORTER application 10386149, Linking neuronal identity transcription factors to neural circuit establishment and maintenance (1F32HD105344-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10386149. Licensed CC0.

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