# Cell type-variation of cytokinesis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $367,229

## Abstract

PROJECT SUMMARY: In animal cells, cytokinesis is driven by constriction of an actomyosin contractile ring,
which is positioned and controlled by signaling from spindle microtubules. It has long been assumed that all
animal cells divide by a similar molecular mechanism. Yet variation in cytokinesis, or diversity in mechanistic
and regulatory pathways, is becoming increasingly clear for different cell types within multicellular organisms.
The mechanisms underlying this cell type-specific regulation of cytokinesis remain poorly understood. In
preliminary studies, we established the C. elegans 4-cell embryo as a system to study cell type-specific
regulation of cytokinesis. At the 4-cell stage, each individual cell already has a unique cell fate, specified by
conserved cell fate signaling pathways (e.g. Src, Wnt/frizzled, Notch/Delta) and dependent on direct cell-cell
contact between specific cell pairs within the embryo. Using either chemical (LatrunculinA) or genetic (formin
temperature sensitive mutant) perturbations to weaken the F-actin contractile ring, we identified cell type-
specific regulation of cytokinesis in the 4-cell embryo. We found that two of the four cells are more protected
against cytokinetic stress than the others and can divide successfully when the F-actin cytoskeleton is
weakened. Embryo micro-dissection and cell pairing experiments revealed that in one of these two protected
cells (P2), cytokinetic protection is cell-intrinsic and dependent on germline fate specification, whereas in the
other protected cell (EMS), cytokinetic protection is cell-extrinsically regulated and requires direct cell-cell
contact with its neighbor cell (P2) and Src-dependent cell-fate signaling. Using our collection of ts mutants, we
also identified cell type-specific protection against cytokinesis failure upon damage to the spindle signaling
machinery in both the 4- and 8-cell embryo. The experiments in this proposal will determine the molecular
mechanisms by which cell fate specification regulates cell type-specific variation in cytokinesis in three ways:
1) we will identify the cellular and molecular mechanisms that underlie cell fate-dependent cytokinetic
protection after actin-based damage; 2) we will compare the cell type-specific protection against cytokinesis
failure after spindle signaling-damage to that after actin-damage in the 4- thru 16-cell embryo and identify
conserved and cell type-specific mechanisms that protect against different cytokinetic stresses; and 3) we will
determine if cell fate specification can also protect cytokinesis from stress in the context of a multicellular
tissue, as well as test whether the principles that apply to the early embryo also apply to mammalian cells in
culture. The proposed experiments will define the role of cell fate signaling in promoting variation in
cytokinesis, identify specific cell fate pathways and test their mechanisms of action, and determine the
universality of cell type-specific variatio...

## Key facts

- **NIH application ID:** 10128459
- **Project number:** 5R01GM117407-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JULIE C CANMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,229
- **Award type:** 5
- **Project period:** 2016-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128459

## Citation

> US National Institutes of Health, RePORTER application 10128459, Cell type-variation of cytokinesis (5R01GM117407-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10128459. Licensed CC0.

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