# Understanding the regulation of neuron cell number and arbor size

> **NIH NIH K99** · NEW YORK UNIVERSITY · 2021 · $140,333

## Abstract

PROJECT SUMMARY/ABSTRACT
How the brain generates the correct number of neurons and how these neurons determine the size of their
arbors to innervate the receptor field is a critical question in neurobiology. The Drosophila visual system is hard
wired and iteratively organized into columns, providing an excellent model to answer these questions.
Drosophila medulla multicolumnar neurons exhibit 5 to 750 neurons per cell type; each neuron class
possesses a distinct morphology and projects its arbors across multiple columns in the optic lobe. The host lab
has obtained single-cell RNA sequencing (scRNAseq) data that determined the transcriptome of almost all
optic lobe neuron cell types throughout development.
The first aim of this project is to understand the molecular and cell biological mechanisms that dictate neuron
number. Under the mentorship of Claude Desplan at New York University (K99 phase), I will perform genetics
experiments that decisively address the role of programmed cell death, neural stem cell division number, and
neuroepithelial size of origin in regulating the number of multicolumnar neurons produced. I will also perform
lineage tracing experiments to determine whether molecularly similar cell types are generated at the same
time. With Holger Knaut at NYU Medical Center, I will learn quantitative live imaging techniques to distinguish
whether neural stem cells divide a limited number of times to generate low-abundance neural classes, or
whether cell fusion of immature progenitors drives cell number.
The second aim of this project is to determine the morphological and genetic processes that dictate the size
and orientation of the arbors of multicolumnar to allow them to cover distinct receptor fields. With the
bioinformatics expertise of Itai Yanai at NYU Medical Center, I will perform RNAseq on adult neurons that are
not numerous enough to be identified in our existing scRNAseq data sets. I will then use machine learning
algorithms to identify these neurons during development in our existing scRNAseq libraries and thus identify
candidate genes required for the regulation of neuron number and arbor size (R00 phase). I will combine these
molecular experiments with live imaging to quantitatively characterize how multicolumnar neurons determine
the orientation and size of their arbors. Preliminary data indicates that cell death and the size of neuroepithelial
region of origin in part dictate multicolumnar neuron number; I have also identified a neuropeptide whose
function is essential for the regulation of neuron arbor size. My work will clarify the molecular basis of neuron
abundance and determine how neurons present in small numbers regulate their arbor size to ensure that their
environment is uniformly sampled, a problem common to many brain regions in most species.

## Key facts

- **NIH application ID:** 10104237
- **Project number:** 1K99EY032269-01
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Jennifer A Malin
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $140,333
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104237

## Citation

> US National Institutes of Health, RePORTER application 10104237, Understanding the regulation of neuron cell number and arbor size (1K99EY032269-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104237. Licensed CC0.

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