# Developmental genetics of neural stem cells

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $299,000

## Abstract

Abstract
In the Drosophila nerve cord, neuronal precursor cells called neuroblasts (NBs) undergo a variable
number of self-renewing asymmetric divisions. At some point during development, these cells either
become quiescent but re-enter cell cycle later, terminally divide into neurons, or undergo apoptosis. No one
knows whether these precursors measure elapsed time or count the number of divisions before exiting the
cell-cycle. In the fly nervous system, NBs differ in their division potential--the number of times they undergo
division. NBs must decide to enter or exit from the cell cycle, but whether their read out is the time elapsed or
a cell cycle count is unknown. Additionally, we do not know whether the mechanism(s) is regulated from
within the cell or extrinsic to the cell. These are difficult questions to address. By examining different types of
NBs, we hope to reveal genes and mechanisms that regulate the cell cycle entry and exit, and the
division potential of NBs during development.
During the course of our work on genetic regulation of asymmetric division of precursors, we isolated a
mutation that caused additional divisions of precursor cells in many lineages in the nerve cord. We
cloned the gene and found that it is a member of the T-box protein family. These proteins play important roles
from development to cancer. Our studies on this gene, midline, led us to believe that it regulates precursor cell
entry and exit from the cell-cycle. It appears to also play a role as part of a mechanism by partnering with
Prospero. Thus, our specific aims are: 1) Determine the role of Mid in the cell cycle entry and exit by
neuronal stem cells, 2) Determine the regulation of mid-expression, whether it is linked to the system
that it regulates or originates outside of the cells it regulates, and 3) Determine if Mid partners with
Prospero to specify the division potential of precursor cells.
The cell cycle entry and exit by precursors and the regulation of their division potential are exceedingly difficult
problems to study. Whether these regulatory mechanisms reside within the cell or extrinsic to cells, do cells
measure the time elapsed, or is there a counting mechanism that determines/interacts with the cell cycle
machinery, are all unknowns. Our aims are focused on exploring these issues using a powerful genetic
system. By no means is this proposal only Mid or Pros-centric, these players are entry points to tackle the
above problems in biology.

## Key facts

- **NIH application ID:** 10241298
- **Project number:** 5R01GM127478-04
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** KRISHNA MOORTHI BHAT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,000
- **Award type:** 5
- **Project period:** 2018-08-16 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241298

## Citation

> US National Institutes of Health, RePORTER application 10241298, Developmental genetics of neural stem cells (5R01GM127478-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241298. Licensed CC0.

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