# Coordination and propagation of cell fate choice in neural circuit assembly

> **NIH NIH F32** · NEW YORK UNIVERSITY · 2021 · $65,994

## Abstract

Project Summary
How vast numbers of neurons are specified into correct cell fates and connected with proper targets during
development represents a fascinating area of developmental neuroscience. Mechanisms of stochastic and
deterministic cell specification programs to achieve neuronal diversity have been extensively studied. Over the
last decades, a number of cell surface molecules have also been identified that mediate axon guidance and
connectivity. However, little is known about the coordination between neuronal specification and specific
connectivity patterns, especially when two synaptic partners undergo two different modes of cell specification
(stochastic vs. deterministic). The Drosophila color vision circuit is an appealing model to address this question
due to our deep knowledge of its development, its precise neuronal connectivity, and the availability of
powerful genetic tools for cell-type specific manipulations. In the fly retina, pale (p) and yellow (y) subtypes of
color photoreceptors (R7 and R8) are stochastically specified, whereas their synaptic partners in the optic lobe
are produced through highly deterministic programs. How do stochastically determined p/y R7 and R8 find
their targets that are deterministically specified in the optic lobes? How is this decision propagated to their
downstream targets during circuit formation? What molecules direct these events? Previous work from our lab
has identified Dpr11 and DIPg, which are members of an interacting network of immunoglobulin superfamily
proteins, as critical regulators of the synaptic connection between yR7 and its downstream target. We
hypothesize that different pairs of cell adhesion molecules mediate the matching of other synaptic partners. By
using single-cell RNA sequencing technology, CRISPR gene editing, and sophisticated genetic manipulation in
the Drosophila color vision circuit, we aim to identify cell adhesion molecules that direct synaptic partner
matching and the molecular logic for coordinating between cell-type specification and the synaptic connectivity
at the system level. We will define the synaptic connectivity as well as generate cell-type specific transgenic
reagents and higher-depth transcriptomes of relevant cell types (Aim 1). We will use a candidate approach
combined with transcriptome analysis of sorted targeted neurons of color photoreceptors to identify the
molecules required for synaptic partner matching (Aim 2). We will compare whether a given neuron uses the
same or different molecular codes for matching its pre- and post-synaptic partners. Finally, we will study how
the synaptic partner choices propagate to neurons further downstream by perturbating the cell fates of R7 and
R8 (Aim 3). Successful completion of this proposal will uncover novel molecular mechanisms regulating
synaptic pairing and probe the fundamental principles underlying the propagation of cell fate choices during
circuit assembly. The principles identified here will be si...

## Key facts

- **NIH application ID:** 10230499
- **Project number:** 1F32EY032750-01
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Yu-Chieh David Chen
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230499

## Citation

> US National Institutes of Health, RePORTER application 10230499, Coordination and propagation of cell fate choice in neural circuit assembly (1F32EY032750-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10230499. Licensed CC0.

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