GO:1990386 mitotic cleavage furrow ingression: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1990386 mitotic cleavage furrow ingression describes the inward advancement of the cleavage furrow from the cell surface toward the center, acting as a purse string that partitions the cytoplasm between daughter cells.
• The process is driven by an actomyosin contractile ring whose assembly and constriction depend on microtubule-derived signals and the centralspindlin complex.
• Key regulators include RhoA, ARF6, Fyn kinase, the chromosomal passenger complex, and focal adhesion components that shape furrow geometry.
• Defective furrow ingression is linked to failed cytokinesis, binucleation, and diseases such as cancer and cardiomyocyte pathology.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal testing of genes controlling furrow ingression.
• Advanced imaging, proteomics, and CRISPR library screening are core methods for dissecting the molecular machinery of furrow ingression.
Description
Mitotic cleavage furrow ingression (GO:1990386) is the biological process in which the cleavage furrow advances from the outer surface of a dividing cell inward toward the cell center, functioning as a purse string that draws tight to separate daughter cells during cytokinesis. This inward movement partitions the cytoplasm and ultimately leaves a thin cytoplasmic bridge before abscission. The process is fundamental to animal cell division and has been studied for decades as a model of mechanochemical coupling between microtubules and the actomyosin cytoskeleton. Researchers investigate GO:1990386 to understand how cells faithfully divide, how division errors contribute to disease, and how to target cytokinesis machinery in cancer and regenerative biology. The term is defined in QuickGO as the advancement of the mitotic cleavage furrow from the outside of the cell inward towards the center, with the furrow acting as a purse string to separate daughter cells and partition cytoplasm until a cytoplasmic bridge forms. Because furrow ingression is a dynamic, force-generating process, its study integrates cell biology, biophysics, and genetics.
mitotic cleavage furrow ingression At A Glance
| GO ID | GO:1990386 |
|---|---|
| GO term | mitotic cleavage furrow ingression |
| Ontology | biological_process |
| Synonym | none |
| Major function | Inward advancement of the cleavage furrow to partition cytoplasm during mitotic cytokinesis |
| Related cellular structure | Actomyosin contractile ring and cleavage furrow |
| Key regulators | Centralspindlin, RhoA, ARF6, Fyn kinase, chromosomal passenger complex |
| Disease relevance | Cytokinesis failure, binucleation, cancer, cardiomyocyte pathology |
What Is GO:1990386?
GO:1990386 mitotic cleavage furrow ingression is the biological process in which the cleavage furrow moves from the cell periphery inward toward the cell center during mitosis. The furrow behaves like a purse string that tightens to separate the two daughter cells and divide the cytoplasm between them, continuing until a cytoplasmic bridge is formed. This process is a critical phase of cytokinesis and depends on the contractile actomyosin ring and its regulation by microtubule and signaling cues.
Why Is mitotic cleavage furrow ingression Important in Cell Biology?
Mitotic cleavage furrow ingression is essential for successful cell division and genome stability, as failure to complete furrow ingression can lead to binucleation, aneuploidy, and disease. Understanding GO:1990386 provides insight into fundamental mechanisms of cytokinesis and offers potential targets for cancer therapy and regenerative medicine.
• Ensures equal partitioning of cytoplasm and genetic material between daughter cells.
• Requires precise coordination between microtubules and the actomyosin ring.
• Involves mechanosensitive regulation under confinement, relevant to tissue environments.
• Defects cause binucleation and aberrant mitotic microtubule distribution.
• Linked to cardiomyocyte binucleation and heart disease pathology.
• Provides targets for anti-cancer strategies exploiting cytokinesis vulnerabilities.
• Focal adhesions influence furrow shape and spindle orientation.
• ARF6 GTPase activation is localized to the furrow during ingression.
• Fyn kinase participates in furrow ingression during meiosis and mitosis.
• Centralspindlin is a central regulator of cleavage signaling.
What Happens During mitotic cleavage furrow ingression?
Initiation of furrow formation
In simple terms: The cell decides where to pinch inward.
Furrow formation begins with signals from the mitotic spindle that specify the equatorial region, involving centralspindlin and microtubule legacy. This positioning ensures the furrow forms at the correct site to divide the cell evenly.
Actomyosin ring assembly and contraction
In simple terms: A belt of actin and myosin tightens like a drawstring.
The actomyosin contractile ring assembles at the furrow and generates force for ingression, a process regulated by mechanics and signaling. RhoA and its effectors promote ring assembly and contraction.
Membrane and cytoskeletal remodeling
In simple terms: The cell surface and internal skeleton rearrange to allow pinching.
ARF6 GTPase localizes and activates at the cleavage furrow during ingression, contributing to membrane trafficking and remodeling. Focal adhesions also control furrow shape and spindle tilt, influencing ingression geometry.
Mechanosensitive regulation under confinement
In simple terms: The furrow senses physical forces and adjusts.
The chromosomal passenger complex is mechanoresponsive and sustains furrow ingression under confined conditions, linking physical cues to division fidelity. Fyn kinase is also involved in furrow ingression during meiosis and mitosis.
Completion and cytoplasmic bridge formation
In simple terms: The furrow closes until only a thin bridge remains.
Ingression continues until a cytoplasmic bridge forms, after which abscission separates the daughter cells. Defects in this stage can result in binucleation, as seen in cardiomyocytes with aberrant microtubule distribution and mislocalized RhoA.
Key Genes Involved in GO:1990386 mitotic cleavage furrow ingression
The following genes and proteins are central to mitotic cleavage furrow ingression based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| RhoA | Regulates actomyosin ring assembly and contraction | Mislocalization linked to binucleation |
| ARF6 | GTPase involved in membrane remodeling at furrow | Localizes and activates during ingression |
| Fyn | Kinase involved in furrow ingression in meiosis and mitosis | Regulates cleavage furrow progression |
| IQGAP3 | Scaffold protein for actomyosin ring anchorage | Defective anchorage in cardiomyocyte binucleation |
| Centralspindlin | Complex regulating cleavage signaling | Central to Rappaport's cleavage signaling |
| Chromosomal passenger complex | Mechanoresponsive regulator of furrow ingression | Sustains ingression under confinement |
| Actin | Structural component of contractile ring | Force generation for ingression |
| Myosin II | Motor protein driving ring contraction | Mechanics of cytokinesis |
| Anillin | Scaffold linking actin and myosin | Ring stability and ingression |
| ECT2 | RhoA activator | Furrow specification |
| MgcRacGAP | Part of centralspindlin | Cleavage signaling |
| MKLP1 | Kinesin in centralspindlin | Microtubule bundling at midzone |
| Focal adhesion proteins | Control furrow shape and spindle tilt | Geometric regulation of ingression |
| Plasma membrane lipids | Provide platform for signaling | ARF6-mediated remodeling |
| Microtubules | Deliver cleavage signals | Microtubule legacy in furrow formation |
| Septins | Cytoskeletal filaments at furrow | Ring stabilization |
| Formins | Actin nucleation | Ring assembly |
How Is mitotic cleavage furrow ingression Regulated?
Mitotic cleavage furrow ingression is regulated by mechanosensitive pathways, including the chromosomal passenger complex that responds to physical confinement. Centralspindlin and RhoA signaling are core regulators of furrow initiation and contraction. Focal adhesions modulate furrow shape and spindle tilt, integrating extracellular cues. Fyn kinase activity also contributes to regulation during meiosis and mitosis.
mitotic cleavage furrow ingression and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| RhoA | Cardiomyocyte binucleation, cancer | Knockout or point mutation in cardiomyocytes |
| IQGAP3 | Defective actomyosin ring anchorage | Knockout in cardiac cell lines |
| Fyn | Meiotic and mitotic furrow defects | Kinase-dead knock-in |
| ARF6 | Membrane remodeling defects | Overexpression or knockout |
| Chromosomal passenger complex | Mechanosensitive furrow failure | Knockout of subunits |
Cancer and genomic instability
Defects in cleavage furrow ingression can lead to cytokinesis failure, binucleation, and aneuploidy, which are hallmarks of cancer. Targeting furrow ingression machinery is a potential therapeutic strategy.
Cardiomyocyte binucleation and heart disease
Aberrant mitotic microtubule distribution, mislocalization of RhoA and IQGAP3, and defective actomyosin ring anchorage are associated with cardiomyocyte binucleation and cleavage furrow ingression defects, contributing to cardiac pathology.
Developmental disorders
Proper furrow ingression is essential for normal development; disruption can cause developmental abnormalities due to failed cell division.
From mitotic cleavage furrow ingression-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate furrow ingression? | CRISPR knockout cell line |
| Does a specific mutation affect furrow dynamics? | Point mutation knock-in |
| How does tagged protein localize during ingression? | Tagged knock-in |
| Does overexpression alter furrow timing? | Overexpression cell model |
| Which genes are essential for cytokinesis? | CRISPR library screening |
| How do focal adhesions affect furrow shape? | Knockout of focal adhesion components |
How to Study the mitotic cleavage furrow ingression Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Furrow ingression dynamics | Visualizing actomyosin ring contraction |
| CRISPR knockout | Gene function in ingression | Testing candidate genes |
| Proteomics | Protein composition at furrow | Identifying novel regulators |
| FRET biosensors | RhoA activity | Monitoring signaling at furrow |
| Atomic force microscopy | Mechanical forces | Measuring ingression forces |
| RNA-seq | Transcriptional changes | Pathway analysis |
| High-content screening | Phenotypic defects | Drug discovery |
Live-cell imaging
Live-cell microscopy visualizes furrow ingression dynamics in real time, often using fluorescently tagged actomyosin or membrane markers.
Proteomics and interactomics
Proteomic approaches identify proteins localized to the cleavage furrow and their post-translational modifications during ingression.
CRISPR screening
Genome-wide CRISPR screens uncover genes required for furrow ingression and cytokinesis.
Biophysical measurements
Force measurements and mechanical assays quantify the forces generated during furrow ingression.
How CRISPR Can Be Used to Study GO:1990386 mitotic cleavage furrow ingression
Knockout
CRISPR knockout of genes such as RhoA or IQGAP3 can reveal their essential roles in furrow ingression and cytokinesis.
Point Mutation
Point mutations in Fyn kinase or ARF6 can dissect specific residues required for furrow ingression.
Knock-in
Tagged knock-in of actomyosin or centralspindlin components enables live tracking of furrow dynamics.
Overexpression
Overexpression of mechanoresponsive chromosomal passenger complex components can test their sufficiency in sustaining ingression.
How EDITGENE Supports mitotic cleavage furrow ingression Research
Researchers studying mitotic cleavage furrow ingression-related genes often need to determine whether a candidate gene is causally involved in furrow dynamics or is merely correlated. EDITGENE provides CRISPR-based cell models and screening services to enable such causal experiments.
Contact EDITGENE today to design your custom CRISPR model for mitotic cleavage furrow ingression research.
Frequently Asked Questions About mitotic cleavage furrow ingression
What is mitotic cleavage furrow ingression?
It is the process where the cleavage furrow moves inward from the cell surface to the center, acting as a purse string to separate daughter cells during mitosis.
What genes are involved in mitotic cleavage furrow ingression?
Key genes include RhoA, ARF6, Fyn, IQGAP3, and components of the centralspindlin and chromosomal passenger complexes.
What is the GO ID for mitotic cleavage furrow ingression?
The GO ID is GO:1990386.
How is furrow ingression regulated?
It is regulated by mechanosensitive pathways, centralspindlin, RhoA signaling, and focal adhesions.
What diseases are linked to defective furrow ingression?
Defects are linked to cancer, genomic instability, and cardiomyocyte binucleation.
What methods study furrow ingression?
Live-cell imaging, CRISPR screening, proteomics, and biophysical measurements are commonly used.
What is the role of ARF6 in furrow ingression?
ARF6 localizes and activates at the cleavage furrow to regulate membrane remodeling during ingression.
How does Fyn kinase affect furrow ingression?
Fyn kinase is involved in cleavage furrow ingression during both meiosis and mitosis.
What is centralspindlin's function?
Centralspindlin is a central regulator of cleavage signaling that specifies the furrow site.
Can CRISPR be used to study furrow ingression?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are used to dissect gene function in furrow ingression.
Conclusion
Mitotic cleavage furrow ingression (GO:1990386) is a dynamic, mechanosensitive process essential for cytokinesis and genome stability. Its molecular machinery, including RhoA, ARF6, Fyn, and centralspindlin, offers targets for understanding and treating diseases like cancer and cardiac pathology. CRISPR-based models and advanced imaging continue to illuminate the mechanisms of furrow ingression.
References
- 1. D'Avino PP et al.. 2005. Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy.. J Cell Sci 118(Pt 8):1549-58 PMID: 15811947
- 2. Levi M et al.. 2010. Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis.. Reproduction 140(6):827-34 PMID: 20841362
- 3. Wang C et al.. 2025. The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement.. J Mol Cell Biol 17(4) PMID: 40693957
- 4. Mishima M. 2016. Centralspindlin in Rappaport's cleavage signaling.. Semin Cell Dev Biol 53:45-56 PMID: 26964770
- 5. Taneja N et al.. 2016. Focal adhesions control cleavage furrow shape and spindle tilt during mitosis.. Sci Rep 6:29846 PMID: 27432211
- 6. Robinson DN et al.. 2004. Mechanics and regulation of cytokinesis.. Curr Opin Cell Biol 16(2):182-8 PMID: 15196562
- 7. Schweitzer JK et al.. 2002. Localization and activation of the ARF6 GTPase during cleavage furrow ingression and cytokinesis.. J Biol Chem 277(30):27210-6 PMID: 12016212
- 8. Leone M et al.. 2018. Cardiomyocyte binucleation is associated with aberrant mitotic microtubule distribution, mislocalization of RhoA and IQGAP3, as well as defective actomyosin ring anchorage and cleavage furrow ingression.. Cardiovasc Res 114(8):1115-1131 PMID: 29522098
