# Cellular and molecular mechanisms underlying the formation of sibling cell size asymmetry

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $298,699

## Abstract

Project Abstract/Summary
The human body contains ~ 3.72 x 1013 cells and 200 different cell types. Generating the right number of
cells overall and enough specialized cells is vital for building functional organs and tissues. How developing
organisms generate and maintain cells with specialized functions and fates is a fundamental problem in
biology.
 Asymmetric cell division is an evolutionary conserved mechanism to create sister cells with different
fate. Cell fate differences can be implemented through the formation of unequal sized siblings. This form of
asymmetric cell division – here also referred to as physical asymmetry - is developmentally controlled since
several metazoan cell types actively induce sibling cell size asymmetry or prevent the formation of sibling
cells differing in their size.
 Physical asymmetric cell division can be induced by positioning the cleavage furrow off cell center.
Since the predominant mechanism for cleavage furrow positioning originates from the mitotic spindle,
spindle mispositioning or the generation of spindle asymmetry causes cleavage furrow formation off cell
center. Alternatively, the dynamic behavior of the cell cortex – regulated through DNA-derived, spindle-
dependent or polarity cues – can result in unequal cortical expansion to create different sized siblings.
Naturally, these mechanisms can be applied in different combinations depending on developmental context
and cell type.
 Here, we propose to use Drosophila larval neuroblasts to investigate molecular mechanisms
regulating the dynamic behavior of the cell cortex during asymmetric cell division. Drosophila neuroblasts
are neural stem cells in the fly, dividing asymmetrically by size and fate. We will use this model system to
investigate how cell intrinsic polarity cues, acting in coordination with the cell cycle, control the localization
and activity of actomyosin regulators to establish physical asymmetric cell division. We will also investigate
how mechanical feedback loops influence spindle geometry and thus cleavage furrow positioning cues. We
have implemented and developed a suite of novel and innovative tools to study these aspects in a
developmental context in vivo. For instance, we are taking advantage of Drosophila’s superb genetic
tractability and amenability for live cell imaging not available in other in vivo systems. We further utilize
optogenetic approaches to manipulate the cell cortex with high spatiotemporal control.
 Our long-term goal is to understand the molecular, cellular and biophysical mechanisms underlying
the generation of sibling cell size asymmetry. The respective size of sibling cells underlies stringent
developmental control and has been implicated to regulate cell behavior and fate. Since sibling cell size
asymmetry is – and involved components are – evolutionary conserved, this proposal will guide future
studies in other phyla. The proposed research is also medically significant; several of the molecules under
in...

## Key facts

- **NIH application ID:** 10077303
- **Project number:** 5R01GM126029-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Clemens C Cabernard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,699
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077303

## Citation

> US National Institutes of Health, RePORTER application 10077303, Cellular and molecular mechanisms underlying the formation of sibling cell size asymmetry (5R01GM126029-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077303. Licensed CC0.

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