# Temporal patterning of neural progenitors to generate neural diversity

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $336,152

## Abstract

Generation of neural diversity is a key question in developmental neurobiology. Studies in
both vertebrates and invertebrate model organisms have shown that neural progenitors are
temporally patterned to generate different neural types in a defined order, and this order can be
recapitulated in progenitors cultured in vitro, suggesting an internal clock. However, the
molecule mechanism is not yet clear. The Drosophila medulla is a unique system to address
this question, because the neural progenitors (neuroblasts) at consecutive temporal stages can
be visualized in one image. Recently a novel Temporal cascade of Transcription Factors (TTFs),
Homothorax (Hth), Eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D) and Tailless (Tll),
were found to be expressed sequentially in medulla neuroblasts as they age. Each gene serves
as the ‘master regulator” of the corresponding temporal stage, and control neuron identity. The
temporal transitions between different temporal stages require that one TTF activates the next,
and represses the previous one. The activation of the next TTF’s expression is a gradual
process, and there is a large overlap between successive TTFs in NBs. However, there is a
sharp transition in the neuronal progeny from expressing one TTF to the next with no overlap.
This is critical to generate distinct neural identities in successive temporal stages. This proposal
is addressing two fundamental questions of developmental timing control in neural progenitors:
1) How is the gradual turning on the next TTF in neural progenitors “translated” into a sharp
temporal transition in the progeny? 2) How is the temporal transition regulated to precisely
control the number of neurons born at each stage? The preliminary data suggest a hypothesis
in which the expression of the next TTF is activated gradually in NBs by its preceding TTF in a
cell-cycle dependent way, but the transcription of the next TTF gene is repressed in the progeny
before its protein inherited from the NB reaches a certain threshold to counteract the repression,
and then the transition in the neuronal progeny occurs. Further, preliminary data show that the
progression in the temporal gene cascade does not happen when NBs are arrested in the cell
cycle, suggesting that the temporal progression is not dependent on the absolute time, but the
cell-cycle progression. In summary cell cycle dependent oscillations could serve as the clock,
and the progressive and irreversible temporal gene cascade could serve as the accumulative
record of time with each cell cycle leaving its mark, providing a mechanism to control the
number of neurons born at each temporal stage.

## Key facts

- **NIH application ID:** 10228551
- **Project number:** 5R01EY026965-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Xin Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $336,152
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228551

## Citation

> US National Institutes of Health, RePORTER application 10228551, Temporal patterning of neural progenitors to generate neural diversity (5R01EY026965-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10228551. Licensed CC0.

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