# The conserved transcription factor UNC-30/PITX1-3 coordinates synaptogenesis and cell identity in C. elegans motor neurons

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2021 · $46,036

## Abstract

PROJECT SUMMARY
The overall goal of this proposal is to determine the molecular mechanisms that take place in neurons and
enable them to establish and maintain functional synapses. For this, the ability of presynaptic neurons to
synthesize, package, and release a neurotransmitter must be coordinated with the ability of postsynaptic
neurons to present the correct neurotransmitter receptors. Revealing the molecular mechanism that
coordinates these processes could have biomedical implications since defects in the establishment and
maintenance of functional synapses are linked to severe neurodegenerative disorders in humans. To address
this knowledge gap, C. elegans represents an ideal model to study those mechanisms due to its known
connectome, powerful genetics, and single-cell resolution analysis. Leveraging these tools, the evolutionarily
conserved transcription factor (TF) UNC-30/PITX1-3 has been shown to control neuronal communication
between nerve cord GABAergic (GABA) motor neurons (MNs) and body-wall muscle by directly activating the
expression of GABA biosynthesis genes (e.g., unc-47/VGAT, unc-25/GAD). We obtained data that shows
genetic loss of either unc-30 or madd-4S, a secreted synaptic organizer produced by GABA MNs, results in a
dramatic reduction of GABA-Receptor (GABAR) clustering on the postsynaptic domain (muscle). Moreover, our
preliminary data shows that animals lacking unc-30 gene activity show reduction of madd-4S expression in
GABA MNs. Therefore, we hypothesize that UNC-30 controls both the establishment and maintenance of
functional synapses by directly activating madd-4S and GABA biosynthesis genes. To evaluate this
hypothesis, in Aim 1 I will use madd-4S specific reporters to determine whether UNC-30 directly regulates
madd-4S expression. I will also conduct cross-species rescue experiments to determine whether UNC-30’s
role in regulating madd-4S expression is conserved across phylogeny. In Aim 2 I will take advantage of the
auxin-inducible degron system to selectively deplete UNC-30 at a particular stage throughout development and
determine whether UNC-30 is required to maintain the functionality of synapses. Moreover, our preliminary
data suggest UNC-30 is also required to prevent the adoption of alternative neuronal identities in GABA MNs,
suggesting a dual role: activator of madd-4S and GABA biosynthesis genes, and repressor of alternative
identity genes. In Aim 3, I will examine the hypothesis that distinct regulatory factors dictate UNC-30’s dual
role. This proposal is significant because human mutations in PITX and GABA biosynthesis genes are linked to
neurodegenerative disorders. Also, it addresses a long-standing question in the fields of neuron development
and disease: how do neurons establish and maintain functional synapses. This work is technically innovative in
its use of powerful genetic approaches and implementing novel methods to study TF function in vivo. This
project will provide an excellent training o...

## Key facts

- **NIH application ID:** 10314649
- **Project number:** 1F31NS124277-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Edgar Orlando Correa-Colón
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314649

## Citation

> US National Institutes of Health, RePORTER application 10314649, The conserved transcription factor UNC-30/PITX1-3 coordinates synaptogenesis and cell identity in C. elegans motor neurons (1F31NS124277-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10314649. Licensed CC0.

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