# Regulation of the asymmetric divisions of C. elegans neural progenitors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $333,721

## Abstract

The asymmetric divisions of neural progenitors are an important regulator of neural fate. Studies over the past
20 years have identified mechanisms that distribute developmental potential and orient the spindle in these
divisions. Much less, however, is known about a subset of these divisions that produce daughter cells of
different sizes, what I refer to here as Daughter Cell Size Asymmetry (DCSA). DCSA has been observed in cell
divisions that range from the C. elegans zygote to mouse cortical progenitors. We propose to study DCSA in
the Q.a and Q.p neural progenitors, where it contributes to the apoptotic fate. These cells provide an excellent
model for the study of DCSA because they use two different mechanisms for DCSA: Q.a divides
asymmetrically by a myosin-dependent, spindle-independent mechanism, and Q.p by a spindle-dependent
mechanism. These studies have important implications for human health: dysregulation of cortical progenitor
divisions can result in lissencephaly and microcephaly, and Wnt signaling, which is dysregulated in several
cancers, regulates Q division asymmetry. The overall goal of our studies is to understand how these types of
asymmetric divisions regulated.
Our work has identified both Wnt signaling and the conserved molecules PIG-1, HAM-1 and TOE-2 as playing
crucial roles in DCSA. Our working model proposes that the localization of PIG-1 controls membrane extension
through GTPases of the Rho family and spindle movement through trimeric G proteins. It also proposes that
Wnt signaling regulates both the myosin-dependent, spindle-independent and the spindle-dependent
mechanisms through the PIG-1 and that HAM-1, TOE-2 and MAP kinase signaling switch Wnt signaling from a
default spindle-dependent mechanism to a spindle-independent mechanism. A combination of genetic,
molecular and imaging approaches will be used to test these hypotheses.

## Key facts

- **NIH application ID:** 9910450
- **Project number:** 5R01NS032057-26
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** GIAN GARRIGA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,721
- **Award type:** 5
- **Project period:** 1994-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910450

## Citation

> US National Institutes of Health, RePORTER application 9910450, Regulation of the asymmetric divisions of C. elegans neural progenitors (5R01NS032057-26). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9910450. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*