# Nutrient-dependent regulation of neural stem cell proliferation and neural circuit formation

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $82,134

## Abstract

Our brain is composed of an immense diversity of neurons that are molecularly, morphologically, and
functionally distinct. Understanding how this immense diversity of neuron types is generated and organized to
allow us and other adult animals to carry out such a vast array of complex tasks and behaviors is of great
importance. By far, most of the neurons in our adult brains are generated during development, either directly or
indirectly from the cell divisions of a defined but, rather heterogeneous population of neural stem cells.
Molecular differences exist among neural stem cells based on their location and neural stem cell themselves
can change their intrinsic genetic programs over time. Research outlined in this proposal is geared towards
better understanding of how neural stem cell extrinsic factors integrate with neural stem cell intrinsic factors to
control numbers and types of neurons produced through time and space during development.
 In the Siegrist lab, we use the genetically tractable model organism, Drosophila melanogaster, to
uncover the genetic pathways and molecular mechanisms regulating neural stem cell proliferation decisions,
from quiescence to proliferation, and then termination once development is complete. Our research goals
include gaining a better understanding of how dietary nutrient availability affects neural stem cell proliferation
decisions. In Drosophila, different neural stem cells respond differently to dietary nutrient availability. Most
enter and exit quiescence in a dietary nutrient- and PI3-kinase-dependent manner, except for a small subset.
The neural stem cells that divide continuously independent of dietary nutrient availability are the neural stem
cells that generate neurons important for memory and learning. Through genetic and single cell sequencing
techniques, we are working to identify the intrinsic differences among these neural stem cell types that
distinguish nutrient-dependence versus nutrient-independence. We are also working on determining how
dietary nutrients consumed during development regulate neural stem cell temporal programs and thus types
and numbers of neurons produced. Neural stem cells in Drosophila sequentially express a series of
transcription factors over time that specify the neuron types produced at each cell division. Whether extrinsic
factors, such as nutrient availability affects neuroblast intrinsic temporal programs is currently unknown.
Finally, we are also working to map out the neural circuitry that regulates neural stem cell proliferation
decisions in response to dietary nutrient availability. Altogether, the research outlined here will advance our
understanding of neural stem cell proliferation control during development and how dietary nutrient availability
affects types and numbers of neurons produced. These insights should stimulate new discoveries in
translational stem cell research in the context of normal development and disease states.

## Key facts

- **NIH application ID:** 11112187
- **Project number:** 3R35GM141886-04S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Sarah Elizabeth Siegrist
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $82,134
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11112187

## Citation

> US National Institutes of Health, RePORTER application 11112187, Nutrient-dependent regulation of neural stem cell proliferation and neural circuit formation (3R35GM141886-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11112187. Licensed CC0.

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