GO:0036090 cleavage furrow ingression: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0036090 cleavage furrow ingression is the biological process in which the cleavage furrow advances from the cell surface inward to form a cytoplasmic bridge during cytokinesis.
• The process is driven by actomyosin ring contraction and is tightly coupled to microtubule and chromosomal passenger complex signaling.
• Key molecular players include actin, myosin II, anillin, RhoA, and the chromosomal passenger complex (CPC).
• Calcium spikes and kinase signaling (e.g., Fyn) modulate furrow ingression in different organisms.
• Defects in furrow ingression can lead to binucleation, polyploidy, and are implicated in cancer and megakaryocyte disorders.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) are essential to dissect gene function in furrow ingression.
Description
Cleavage furrow ingression (GO:0036090) is a fundamental step in cytokinesis, the final stage of cell division. During this process, the plasma membrane invaginates at the cell equator, forming a cleavage furrow that constricts inward like a purse string to separate the cytoplasm of the two daughter cells. This mechanical event is highly regulated and requires the coordinated action of the actomyosin cytoskeleton, microtubules, and signaling proteins. Understanding cleavage furrow ingression is critical for researchers studying cell division, developmental biology, and diseases caused by cytokinesis failure, such as cancer and blood disorders. The process has been studied in diverse model organisms, including Dictyostelium, fission yeast, Trypanosoma brucei, and mammalian cells, revealing both conserved and organism-specific mechanisms. Recent work has also highlighted the role of mechanical forces and the chromosomal passenger complex in sustaining furrow ingression under confinement. This article provides a comprehensive overview of the ontology, molecular players, regulatory mechanisms, and research methods for studying GO:0036090.
cleavage furrow ingression At A Glance
| GO ID | GO:0036090 |
|---|---|
| GO term | cleavage furrow ingression |
| Ontology | biological_process |
| Synonym | cleavage furrow contraction |
| Definition | Advancement of the cleavage furrow from the outside of the cell inward towards the center of the cell, forming a cytoplasmic bridge. |
| Major function | Separation of daughter cells during cytokinesis by actomyosin-driven membrane invagination. |
| Related processes | Cytokinesis, actomyosin ring contraction, cell division. |
| Key cellular components | Actomyosin ring, plasma membrane, microtubules, chromosomal passenger complex. |
What Is GO:0036090?
Cleavage furrow ingression (GO:0036090) is defined as the advancement of the cleavage furrow from the outside of the cell inward towards the center of the cell. The cleavage furrow acts as a purse string that draws tight to separate daughter cells during cytokinesis and partition the cytoplasm between the two daughter cells. The furrow ingresses until a cytoplasmic bridge is formed.
Why Is cleavage furrow ingression Important in Cell Biology?
Cleavage furrow ingression is essential for successful cell division and genome stability. Failure of this process leads to cytokinesis defects, resulting in binucleated or polyploid cells, which are hallmarks of cancer and certain hematological disorders. Moreover, the mechanical forces and signaling pathways that control furrow ingression are conserved across eukaryotes, making it a valuable model for studying fundamental cell biology. Research on GO:0036090 also informs developmental biology, as precise cell division is required for tissue morphogenesis and organismal development.
• Ensures equal segregation of genetic material and cytoplasmic contents during cell division.
• Defects in furrow ingression cause binucleation and polyploidy, contributing to tumorigenesis.
• Required for megakaryocyte maturation and platelet production; endomitotic megakaryocytes show furrow regression.
• Calcium signaling and kinase cascades (e.g., Fyn) regulate furrow ingression in meiosis and mitosis.
• The chromosomal passenger complex (CPC) mechanoresponds to sustain furrow ingression under confinement.
• Conserved mechanisms in Trypanosoma brucei and fission yeast offer insights into divergent cytokinesis.
• Provides targets for anti-parasitic drug development (e.g., Trypanosoma KLIF-associated proteins).
• Serves as a model for studying mechanotransduction and cytoskeletal dynamics.
• Implicated in developmental disorders due to cytokinesis failure.
• Enables high-throughput screening for cytokinesis inhibitors or modulators.
What Happens During cleavage furrow ingression?
Initiation and Positioning of the Cleavage Furrow
In simple terms: The cell decides where to pinch in two.
The cleavage furrow is positioned at the cell equator through signals from the mitotic spindle and the chromosomal passenger complex (CPC). Microtubules deliver regulatory factors that specify the furrow site. In Trypanosoma brucei, KLIF-associated cytoskeletal proteins promote furrow positioning and ingression. In fission yeast, septation is guided by the actomyosin ring and associated proteins.
Actomyosin Ring Assembly and Contraction
In simple terms: A belt of actin and myosin tightens to pull the membrane inward.
The actomyosin ring, composed of actin filaments and myosin II, assembles at the equatorial cortex. Its contraction provides the force for furrow ingression. In Dictyostelium, myosin II is essential for furrow ingression. RhoA signaling activates formins and ROCK to promote actin polymerization and myosin activation.
Membrane Remodeling and Cytoplasmic Bridge Formation
In simple terms: The membrane narrows until a thin bridge connects the two new cells.
As the actomyosin ring contracts, the plasma membrane is remodeled and additional membrane is delivered to accommodate the increasing surface curvature. The furrow ingresses until a cytoplasmic bridge forms, which is later resolved by abscission. Calcium spikes accompany furrow ingression and cell separation in fission yeast, suggesting a role for calcium signaling in membrane dynamics.
Regulation by Kinases and the Chromosomal Passenger Complex
In simple terms: Special proteins act as brakes and accelerators to ensure the pinch is done correctly.
The CPC, including Aurora B kinase, regulates furrow ingression and abscission. Under mechanical confinement, the CPC becomes mechanoresponsive to sustain furrow ingression. Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis in mammalian cells. In endomitotic megakaryocytes, furrow ingression can be followed by regression, indicating checkpoint control.
Completion and Abscission
In simple terms: The bridge is cut to fully separate the two cells.
After furrow ingression, the cytoplasmic bridge is resolved by abscission, a process requiring ESCRT machinery and membrane fission. Defects in abscission lead to binucleation. The entire process is tightly coordinated with chromosome segregation and cell cycle progression.
Key Genes Involved in GO:0036090 cleavage furrow ingression
The following genes and proteins are key players in cleavage furrow ingression, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACTB | Actin filament component of actomyosin ring | Essential for furrow contraction; knockout causes cytokinesis failure |
| MYH9 | Myosin II heavy chain; motor for ring contraction | Mutations linked to platelet disorders; knockout impairs ingression |
| RHOA | GTPase regulating actomyosin assembly | Key upstream regulator; overexpression enhances furrow ingression |
| ANLN | Anillin; scaffolds actomyosin ring to membrane | Knockdown causes furrow instability |
| AURKB | Aurora B kinase; CPC component | Regulates furrow ingression and abscission; inhibition blocks cytokinesis |
| INCENP | CPC component; activates Aurora B | Required for furrow ingression under confinement |
| FYN | Src-family kinase | Involved in furrow ingression during meiosis and mitosis |
| KLIF | Kinetoplastid-specific protein | Promotes furrow positioning and ingression in Trypanosoma brucei |
| CDC15 | Fission yeast kinase | Regulates septation and furrow ingression |
| MID1 | Fission yeast anillin-like protein | Required for actomyosin ring positioning |
| RLC | Myosin regulatory light chain | Phosphorylation controls myosin activity during ingression |
| EZR | Ezrin; links actin to membrane | Facilitates membrane remodeling during furrow ingression |
| RACGAP1 | Rho GTPase activating protein | Regulates RhoA activity at the furrow |
| PLK1 | Polo-like kinase 1 | Controls actomyosin ring assembly and furrow ingression |
| CEP55 | Centrosomal protein; midbody component | Required for abscission after ingression |
| CHMP4B | ESCRT-III component | Mediates membrane scission during abscission |
| SPTAN1 | Spectrin; membrane skeleton | Maintains membrane integrity during furrow ingression |
| CALM1 | Calmodulin; calcium sensor | Mediates calcium signaling during furrow ingression |
How Is cleavage furrow ingression Regulated?
Cleavage furrow ingression is regulated by multiple signaling pathways. The chromosomal passenger complex (CPC) acts as a mechanosensor to sustain furrow ingression under mechanical confinement. Calcium spikes accompany furrow ingression and cell separation in fission yeast, suggesting calcium-calmodulin signaling modulates actomyosin contraction. Fyn kinase activity is required for efficient furrow ingression during meiosis and mitosis. In endomitotic megakaryocytes, furrow ingression can be reversed by furrow regression, indicating checkpoint control. RhoA and its effectors (ROCK, formins) are central regulators of actomyosin ring assembly and contraction.
cleavage furrow ingression and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AURKB | Cancer, cytokinesis failure | Knockout or point mutation in cancer cell lines |
| MYH9 | Thrombocytopenia, hearing loss | Knock-in of MYH9 mutations in iPSCs |
| KLIF | Trypanosomiasis | Knockout in Trypanosoma brucei |
| FYN | Developmental disorders | Knockout mouse models |
| ANLN | Cancer, cytokinesis defects | Overexpression in HeLa cells |
Cancer and Genome Instability
Defects in cleavage furrow ingression lead to cytokinesis failure, resulting in binucleated and polyploid cells, which are common in many cancers. Aurora B kinase (AURKB) overexpression is associated with tumor progression, and its inhibition causes furrow ingression defects. Targeting furrow ingression components is a potential therapeutic strategy.
Megakaryocyte Disorders and Thrombocytopenia
Endomitotic megakaryocytes that form a bipolar spindle exhibit cleavage furrow ingression followed by furrow regression, a process linked to platelet production. Disruption of this process can lead to thrombocytopenia.
Parasitic Infections
Trypanosoma brucei cytokinesis relies on KLIF-associated cytoskeletal proteins for furrow positioning and ingression. These proteins are potential drug targets for African sleeping sickness.
Developmental Disorders
Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis; its dysregulation may contribute to developmental defects.
From cleavage furrow ingression-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate furrow ingression? | Knockout cell line (e.g., HeLa, U2OS) |
| Does a specific mutation affect furrow ingression? | Point mutation knock-in via CRISPR |
| Where does protein X localize during ingression? | Tagged knock-in (e.g., GFP) |
| Does overexpression of gene Y enhance ingression? | Overexpression cell line |
| What is the role of gene Z in parasite cytokinesis? | Knockout in Trypanosoma brucei |
| How does mechanical confinement affect ingression? | Microfluidic confinement with CPC mutants |
How to Study the cleavage furrow ingression Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Furrow ingression dynamics | Real-time visualization in mammalian cells |
| CRISPR knockout | Gene requirement for ingression | Functional screening |
| RNAi | Gene knockdown effects | Phenotypic analysis |
| Proteomics | Protein interactions at furrow | Identifying novel components |
| Calcium imaging | Calcium signaling during ingression | Fission yeast cytokinesis |
| FRET biosensors | RhoA activity at furrow | Spatiotemporal regulation |
| Electron microscopy | Ultrastructure of furrow | Membrane remodeling |
| Microfluidic confinement | Mechanical stress response | CPC mechanosensing |
Live-Cell Imaging
Live-cell imaging with fluorescently tagged actomyosin or membrane markers allows real-time visualization of furrow ingression dynamics. This method is widely used to quantify ingression rate and identify defects.
RNA Interference and CRISPR Knockout
RNAi and CRISPR knockout are used to deplete candidate genes and assess their requirement for furrow ingression. For example, knockout of AURKB or ANLN causes furrow ingression failure.
Proteomics and Interactomics
Proteomic approaches identify proteins associated with the cleavage furrow. KLIF-associated cytoskeletal proteins were identified in Trypanosoma brucei using proteomics.
Calcium Imaging
Genetically encoded calcium indicators reveal calcium spikes during furrow ingression in fission yeast.
How CRISPR Can Be Used to Study GO:0036090 cleavage furrow ingression
Knockout
CRISPR knockout of genes such as AURKB, ANLN, or MYH9 is used to test their essentiality for cleavage furrow ingression. Knockout cells typically exhibit failed ingression, binucleation, or polyploidy.
Point Mutation
Point mutations in genes like FYN or MYH9 can be introduced via CRISPR to model disease-associated variants and assess their impact on furrow ingression.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous loci allows visualization of protein localization during furrow ingression without overexpression artifacts.
Overexpression
Overexpression of genes like RHOA or ANLN can enhance or disrupt furrow ingression, providing gain-of-function insights.
How EDITGENE Supports cleavage furrow ingression Research
Researchers studying cleavage furrow ingression-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated. EDITGENE provides CRISPR-based services to generate precisely engineered cell models for functional validation.
Contact EDITGENE today to design your custom CRISPR model for cleavage furrow ingression research.
Frequently Asked Questions About cleavage furrow ingression
What is cleavage furrow ingression?
Cleavage furrow ingression (GO:0036090) is the process by which the cleavage furrow advances inward to separate daughter cells during cytokinesis.
What genes are involved in cleavage furrow ingression?
Key genes include ACTB, MYH9, RHOA, ANLN, AURKB, and FYN, among others.
What is the role of the chromosomal passenger complex in furrow ingression?
The CPC, including Aurora B kinase, regulates furrow ingression and mechanoresponds to sustain it under confinement.
How is cleavage furrow ingression studied?
It is studied using live-cell imaging, CRISPR knockout, RNAi, proteomics, and calcium imaging.
What happens if cleavage furrow ingression fails?
Failure leads to binucleation, polyploidy, and is associated with cancer and megakaryocyte disorders.
Is cleavage furrow ingression conserved across species?
Yes, core mechanisms are conserved, but specific proteins like KLIF are unique to Trypanosoma brucei.
What is the role of calcium in furrow ingression?
Calcium spikes accompany furrow ingression and cell separation in fission yeast.
How does Fyn kinase affect furrow ingression?
Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis.
What are the best model systems for studying furrow ingression?
Common models include mammalian cell lines, fission yeast, Dictyostelium, and Trypanosoma brucei.
Can CRISPR be used to study furrow ingression?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are powerful tools for dissecting gene function in furrow ingression.
Conclusion
Cleavage furrow ingression (GO:0036090) is a critical biological process that ensures proper cell division. Its regulation involves a complex interplay of cytoskeletal, signaling, and mechanical factors. Understanding this process has broad implications for cancer, developmental biology, and infectious diseases. CRISPR-based models and advanced imaging techniques continue to unravel the molecular details, offering potential therapeutic targets.
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. Weber I. 2001. On the mechanism of cleavage furrow ingression in Dictyostelium.. Cell Struct Funct 26(6):577-84 PMID: 11942612
- 3. Zhou Q et al.. 2022. KLIF-associated cytoskeletal proteins in Trypanosoma brucei regulate cytokinesis by promoting cleavage furrow positioning and ingression.. J Biol Chem 298(6):101943 PMID: 35447115
- 4. Cortés JC et al.. 2016. Fission yeast septation.. Commun Integr Biol 9(4):e1189045 PMID: 27574536
- 5. Poddar A et al.. 2021. Calcium spikes accompany cleavage furrow ingression and cell separation during fission yeast cytokinesis.. Mol Biol Cell 32(1):15-27 PMID: 33175606
- 6. Levi M et al.. 2010. Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis.. Reproduction 140(6):827-34 PMID: 20841362
- 7. Geddis AE et al.. 2007. Endomitotic megakaryocytes that form a bipolar spindle exhibit cleavage furrow ingression followed by furrow regression.. Cell Cycle 6(4):455-60 PMID: 17312391
- 8. Wang C et al.. 2025. The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement.. J Mol Cell Biol 17(4) PMID: 40693957
