# Molecular determinants of synaptic specificity underlying a visuomotor transformation

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $109,878

## Abstract

Project Summary
Visuomotor transformation (VMT), a vital process by which the brain converts vision into action, requires precise
synaptic connectivity between sensory and motor neural circuits. Impaired visuomotor processing has been
associated with a wide range of neurological disorders. Developmental and molecular origins of a VMT remain
elusive due to the lack of experimentally tractable model systems. I address this knowledge gap by interrogating
the visuomotor interface of Drosophila, where transcriptomics, connectomics and physiology can be integrated to
causally link genes and molecules with circuit structure and function. My recent work uncovered a completely new
wiring strategy underlying a VMT: visual space coordinates are transformed into synaptic weights. Such synaptic
gradient mechanism found in Visual Projection Neurons (VPN) emerges through within-cell-type synaptic
specificity. Individual neurons belonging to the same VPN cell type connect to different postsynaptic partners,
which elicits multidirectional motor programs in response to differentially localized visual stimuli. Aim 1 of my
research during the K99 phase will build on these findings and identify the transcriptomic signatures of synaptic
gradients. I hypothesize that within-cell-type synaptic specificity is achieved through transcriptomic uniqueness of
individual neurons of the same type (i.e., molecular gradients of wiring genes). In collaboration with my co-mentor
Dr. Y. Kurmangaliyev, I will test this hypothesis and generate a developmental transcriptomic atlas of the fly
visuomotor interface featuring 20 VPN cell types. Single-cell RNA-seq profiling will be followed by the validation of
candidate gene expression patterns using genetics and spatial transcriptomics. This will generate a molecular
model of synaptic gradients. Aim 2, pursued in collaboration with my co-mentor Dr. C. von Reyn, will functionally
test this model using genetic perturbation screening. Candidate genes will be misexpressed in VPNs and their
postsynaptic partners, and the effects on synaptic gradients will be assessed using electrophysiology. This work
will provide causal relationships between molecular gradients of wiring genes and within-cell-type synaptic
specificity. The mentorship I will continue to receive from Dr. Zipursky, and the training in single-cell data analysis
and electrophysiology I will acquire during the K99 phase will facilitate my transition to an independent research
program. Aim 3, to be pursued during the R00 phase, will investigate the gene regulatory networks of synaptic
specificity in visuomotor circuits. I will examine the role of global extrinsic regulatory programs (e.g., spatially graded
Wnt signaling and neural activity) in establishing synaptic gradients using a combination of Perturb-RNA-seq and
chromatin accessibility (ATAC-seq) analysis in VPNs. This approach will link extracellular signals with transcription
factor mediated differential gene expression in a...

## Key facts

- **NIH application ID:** 10864704
- **Project number:** 1K99EY036123-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Mark Dombrovskiy
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $109,878
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864704

## Citation

> US National Institutes of Health, RePORTER application 10864704, Molecular determinants of synaptic specificity underlying a visuomotor transformation (1K99EY036123-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10864704. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*