# Temporal Patterning of Neural Progenitors to Generate Neural Diversity

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $373,337

## Abstract

Vertebrate and invertebrate neural progenitors are temporally patterned to generate a great
diversity of neural types in a birth-order dependent manner. Series of temporal transcription
factors (TTF) were found to be sequentially expressed in Drosophila neuroblasts, and they are
proposed to form transcriptional cascades to control the sequential generation of different neural
types. However, whether the cross-regulations inferred from mutant phenotypes are direct
transcriptional regulations haven't been demonstrated. Furthermore, the cross-regulations
among TTFs are often not sufficient for the temporal transitions, suggesting other mechanisms
are at play to regulate the temporal progression. We use the Drosophila medulla neuroblasts to
study these questions. In the previous R01 period, we identified molecular mechanisms
controlling transitions to the Slp and Ey temporal stages, and also identified a comprehensive
list of novel temporal transcription factors through single-cell RNA sequencing. In this renewal
application, we present our preliminary data of single-nuclear ATAC seq, which revealed the
dynamic chromatin accessibility during temporal patterning of medulla neuroblasts. Through
analyzing the differentially accessible regions, we identified the possible enhancers controlling
the temporal expression patterns of TTF genes. Through integration of scRNA-seq and
snATACseq and a combination of reporter assays, genetic analysis and Dam-ID experiments,
we propose to elucidate the transcriptional regulatory networks controlling the sequential
temporal transitions in great detail. Furthermore, we found that different epigenetic factors are
required at different steps of temporal patterning. We propose to further examine how they
regulate the dynamic chromatin accessibility and how they are recruited to specific target genes
during temporal patterning. Finally, we propose to examine the fundamental molecular
mechanisms that coordinate the growth/proliferation with TTF cascade progression, and will test
our hypothesis that early TTFs have different roles in controlling growth/proliferation than late
TTFs through a combination of approaches.

## Key facts

- **NIH application ID:** 10690023
- **Project number:** 5R01EY026965-07
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Xin Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $373,337
- **Award type:** 5
- **Project period:** 2017-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690023

## Citation

> US National Institutes of Health, RePORTER application 10690023, Temporal Patterning of Neural Progenitors to Generate Neural Diversity (5R01EY026965-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690023. Licensed CC0.

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