GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development: Regulatory Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061052 describes a biological process that restrains cardiomyocyte growth during heart development, ensuring the heart reaches its correct size and architecture.
• This process is distinct from pathological hypertrophy; it operates during developmental windows to limit excessive cell growth and maintain cardiac muscle cell maturation.
• MicroRNAs, particularly miR-1, and RNA-binding proteins such as G3bp1 are key regulators of cardiomyocyte growth and hypertrophy.
• Autophagy and metabolic adaptation are tightly linked to cardiomyocyte health and growth control during development.
• Disruption of negative growth regulation can lead to cardiac developmental defects, as shown by Pr72 deletion in zebrafish.
• CRISPR-based models (knockout, knock-in, overexpression) enable precise interrogation of genes controlling this process in cardiac cells.
Description
The Gene Ontology term GO:0061052, negative regulation of cell growth involved in cardiac muscle cell development, defines a biological process that restricts the growth of cardiac muscle cells during heart formation. This process is essential for proper heart morphogenesis, as uncontrolled cardiomyocyte growth can lead to structural defects and impaired cardiac function. Understanding this term helps researchers dissect the molecular brakes that coordinate heart size and cellular maturation. The process is not merely a passive brake; it integrates developmental cues, microRNA networks, and metabolic signals to ensure that cardiac muscle cells stop growing at the right time and place. This article synthesizes published findings on the genes, mechanisms, and experimental models used to study GO:0061052, providing a resource for researchers designing CRISPR-based experiments to probe cardiac growth regulation.
negative regulation of cell growth involved in cardiac muscle cell development At A Glance
| GO ID | GO:0061052 |
|---|---|
| GO term | negative regulation of cell growth involved in cardiac muscle cell development |
| Ontology | biological_process |
| Synonym | none |
| Major function | Restricts cardiomyocyte growth during heart development to ensure correct heart size and morphology |
| Related processes | Cardiac muscle cell development, regulation of cell growth, microRNA-mediated gene silencing |
| Key regulators | miR-1, G3bp1, Pr72, autophagy-related genes |
| Disease relevance | Cardiac developmental defects, cardiomyopathies, hypertrophy |
| Experimental models | Zebrafish, mouse, and CRISPR-engineered cell lines |
What Is GO:0061052?
GO:0061052 is a biological process that negatively regulates cell growth specifically in the context of cardiac muscle cell development. It encompasses any mechanism that limits the increase in cardiomyocyte size or number during heart development, ensuring proper organ size and function. This term is distinct from general growth suppression because it is spatially and temporally restricted to cardiac muscle cells and their developmental program.
Why Is negative regulation of cell growth involved in cardiac muscle cell development Important in Cell Biology?
GO:0061052 is critical because it provides a molecular framework for understanding how the heart limits cardiomyocyte growth during development, a process that, when disrupted, leads to congenital heart defects and contributes to later-life cardiac disease. Researchers studying cardiac regeneration and hypertrophy need to know the brakes on growth to manipulate them therapeutically.
• Prevents excessive cardiomyocyte growth that could impair heart chamber formation.
• Coordinates developmental timing of cardiac muscle cell maturation.
• Involves microRNA networks, notably miR-1, which are dysregulated in cardiac hypertrophy.
• Links to autophagy and metabolic adaptation, key determinants of cardiomyocyte health.
• Disruption causes cardiac developmental defects in model organisms such as zebrafish.
• Provides targets for CRISPR-based screens to identify novel growth regulators.
• Relevant to understanding congenital heart disease and pediatric cardiomyopathies.
• Informs strategies for promoting cardiac regeneration by temporarily lifting growth brakes.
• Helps explain sex- and context-dependent differences in cardiac growth.
• Offers a paradigm for studying negative regulation in other muscle cell types.
What Happens During negative regulation of cell growth involved in cardiac muscle cell development?
Initiation of growth restriction signals
In simple terms: The heart sends signals to tell muscle cells to stop growing too much.
During cardiac development, extracellular and intracellular cues activate pathways that limit cardiomyocyte growth. MicroRNAs such as miR-1 are induced and target growth-promoting transcripts, while RNA-binding proteins like G3bp1 modulate microRNA availability. This initiation phase sets the stage for downstream growth suppression.
MicroRNA-mediated silencing of growth genes
In simple terms: Small RNA molecules block the production of proteins that make cells grow.
miR-1 and other microRNAs bind to complementary sequences in mRNAs encoding growth factors and cell cycle regulators, leading to translational repression or degradation. This silencing reduces the levels of proteins that drive cardiomyocyte proliferation and hypertrophy. The G3bp1-miR-1 axis has been shown to regulate cardiomyocyte hypertrophy, highlighting the importance of RNA-binding proteins in this process.
Autophagy and metabolic adaptation
In simple terms: Cells recycle their own components to stay healthy and limit growth.
Autophagy is a catabolic process that degrades damaged organelles and proteins, providing energy and limiting cell growth. In cardiomyocytes, autophagy adapts to metabolic changes and contributes to negative regulation of growth during development. This mechanism ensures that cardiac muscle cells maintain homeostasis and do not undergo unchecked expansion.
Integration with developmental timing
In simple terms: The stop-growing signal is timed with the heart's developmental schedule.
Negative regulation of cell growth is coordinated with other developmental processes such as chamber specification and valve formation. For example, deletion of Pr72 in zebrafish causes cardiac developmental defects, indicating that proper timing of growth restriction is essential. This integration ensures the heart reaches its correct size and shape.
Key Genes Involved in GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
The following genes and proteins have been implicated in negative regulation of cell growth during cardiac muscle cell development, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| miR-1 | MicroRNA that represses growth-promoting transcripts | Key regulator of cardiomyocyte hypertrophy and development |
| G3bp1 | RNA-binding protein modulating miR-1 activity | Regulates cardiomyocyte hypertrophy via miR-1 axis |
| Pr72 | Protein phosphatase 2A regulatory subunit | Deletion causes cardiac developmental defects in zebrafish |
| mTOR | Kinase integrating growth signals | Central regulator of cell growth, often targeted in cardiac studies |
| AMPK | Energy sensor kinase | Links metabolic status to growth suppression |
| Beclin-1 | Autophagy initiation protein | Mediates autophagy-related growth restriction |
| LC3 | Autophagosome marker | Used to monitor autophagy in cardiomyocytes |
| Atg5 | Autophagy-related protein | Essential for autophagy and growth control |
| Atg7 | Autophagy-related protein | Required for autophagosome formation |
| FoxO | Transcription factor | Promotes autophagy and inhibits growth |
| p53 | Tumor suppressor | Can limit cell growth under stress |
| Myc | Transcription factor | Drives growth; its repression contributes to negative regulation |
| Cyclin D1 | Cell cycle regulator | Target of microRNA-mediated silencing |
| CDK4 | Cell cycle kinase | Involved in cardiomyocyte proliferation control |
| VEGF | Angiogenic factor | Indirectly influences cardiac growth via angiogenesis |
| miR-133 | MicroRNA | Modulates cardiac hypertrophy |
| Hand2 | Transcription factor | Essential for cardiac development; may interact with growth pathways |
How Is negative regulation of cell growth involved in cardiac muscle cell development Regulated?
The process is regulated by a network of microRNAs, RNA-binding proteins, and metabolic sensors. miR-1 and G3bp1 form an axis that controls cardiomyocyte hypertrophy. Autophagy, regulated by AMPK, mTOR, and FoxO, provides a catabolic brake on growth. Developmental signals such as Pr72 also modulate this process. Additionally, VEGF signaling influences cardiac growth indirectly through angiogenesis.
negative regulation of cell growth involved in cardiac muscle cell development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Pr72 | Cardiac developmental defects | Zebrafish knockout |
| miR-1 | Cardiomyocyte hypertrophy | Mouse overexpression/knockout |
| G3bp1 | Cardiac hypertrophy | CRISPR knockout in cardiomyocytes |
| mTOR | Hypertrophy and heart failure | Conditional knockout mouse |
| Beclin-1 | Autophagy-related cardiac disease | Knockout mouse |
Cardiac developmental defects
Disruption of negative growth regulation during heart development can cause structural abnormalities. For example, deletion of Pr72 in zebrafish leads to cardiac developmental defects, highlighting the importance of this process in normal heart formation.
Cardiomyocyte hypertrophy and heart failure
Loss of growth-suppressive mechanisms, such as dysregulation of miR-1 or G3bp1, contributes to pathological cardiomyocyte hypertrophy, a precursor to heart failure. Understanding GO:0061052 may inform therapies that restore growth control.
Neuromuscular disorders
While primarily cardiac, muscle satellite cell dysfunction in neuromuscular disorders shares molecular features with impaired growth regulation, suggesting broader relevance of growth control pathways.
From negative regulation of cell growth involved in cardiac muscle cell development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate cardiomyocyte growth? | CRISPR knockout in iPSC-derived cardiomyocytes |
| What is the effect of a point mutation in gene Y? | CRISPR point mutation knock-in in zebrafish |
| How does overexpression of gene Z affect heart size? | Transgenic overexpression in mouse |
| Where is protein W localized during development? | Tagged knock-in in cardiomyocytes |
| Which microRNAs mediate growth suppression? | CRISPR library screening for microRNA genes |
| Does autophagy mediate growth restriction? | Knockout of autophagy genes in cardiac cells |
How to Study the negative regulation of cell growth involved in cardiac muscle cell development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptome changes | Identify growth-related gene networks |
| Proteomics | Protein abundance and modifications | Validate microRNA targets |
| Confocal imaging | Cardiac morphology and cell size | Assess developmental defects |
| Autophagy flux assay | Autophagic degradation | Link autophagy to growth control |
| CRISPR screen | Gene function at scale | Discover novel growth regulators |
| qPCR | MicroRNA and mRNA levels | Validate expression changes |
| Western blot | Protein expression | Confirm knockout/overexpression |
| Histology | Tissue architecture | Evaluate heart defects |
Transcriptomic profiling
RNA-seq can identify changes in gene expression when negative growth regulators are perturbed, revealing downstream targets and pathways.
Proteomic analysis
Mass spectrometry-based proteomics quantifies protein abundance and modifications, helping to uncover post-transcriptional effects of microRNAs and RNA-binding proteins.
Imaging of cardiac morphology
High-resolution imaging in zebrafish and mouse models visualizes heart size, chamber architecture, and cellular growth defects upon gene manipulation.
Autophagy flux assays
LC3 turnover and tandem fluorescent reporters measure autophagic activity, linking autophagy to growth regulation.
How CRISPR Can Be Used to Study GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
Knockout
CRISPR knockout of candidate genes such as G3bp1 or Pr72 in cardiomyocytes or model organisms can reveal their necessity in negative growth regulation.
Point Mutation
Introducing specific point mutations via CRISPR base editing or HDR can model human variants and dissect domain-specific functions in growth suppression.
Knock-in
Knock-in of fluorescent tags or reporter cassettes allows real-time tracking of protein localization and dynamics during cardiac development.
Overexpression
CRISPR activation or transgenic overexpression of growth-suppressive genes like miR-1 can test sufficiency in limiting cardiomyocyte growth.
How EDITGENE Supports negative regulation of cell growth involved in cardiac muscle cell development Research
Researchers studying negative regulation of cell growth involved in cardiac muscle cell development-related genes often need to determine whether a candidate gene is causally involved in restricting cardiomyocyte growth. EDITGENE provides a comprehensive suite of CRISPR services to enable such investigations, from knockout to overexpression and library screening.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of cell growth involved in cardiac muscle cell development research.
Frequently Asked Questions About negative regulation of cell growth involved in cardiac muscle cell development
What is GO:0061052?
GO:0061052 is a Gene Ontology biological process term for negative regulation of cell growth involved in cardiac muscle cell development, describing mechanisms that limit cardiomyocyte growth during heart formation.
What genes are involved in negative regulation of cell growth involved in cardiac muscle cell development?
Key genes include miR-1, G3bp1, Pr72, and autophagy-related genes such as Beclin-1 and Atg5.
How does miR-1 regulate cardiomyocyte growth?
miR-1 represses growth-promoting transcripts and its axis with G3bp1 controls cardiomyocyte hypertrophy.
What diseases are linked to defects in this process?
Cardiac developmental defects and cardiomyocyte hypertrophy are linked to disruption of this process.
What model organisms are used to study GO:0061052?
Zebrafish and mouse models are commonly used, along with CRISPR-engineered cell lines.
How can CRISPR help study this process?
CRISPR knockout, knock-in, point mutation, and overexpression models allow precise manipulation of candidate genes to test their role in growth regulation.
Is autophagy involved in negative regulation of cardiac cell growth?
Yes, autophagy provides a catabolic brake on cardiomyocyte growth and is regulated by AMPK, mTOR, and FoxO.
What is the role of Pr72 in cardiac development?
Pr72 deletion in zebrafish causes cardiac developmental defects, indicating its importance in proper heart formation.
How is G3bp1 related to cardiac hypertrophy?
G3bp1 modulates miR-1 activity, and its dysregulation contributes to cardiomyocyte hypertrophy.
What experimental methods are used to study this process?
RNA-seq, proteomics, imaging, autophagy flux assays, and CRISPR screens are commonly employed.
Conclusion
GO:0061052 represents a critical biological process that restrains cardiomyocyte growth during heart development, with implications for congenital heart defects and cardiac hypertrophy. Key regulators such as miR-1, G3bp1, and autophagy-related proteins have been identified through published studies. Leveraging CRISPR-based models and multi-omics approaches will further elucidate the mechanisms and therapeutic potential of this process.
References
- 1. Ganassi M et al.. 2022. Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.. Eur J Transl Myol 32(1) PMID: 35302338
- 3. Callis TE et al.. 2007. MicroRNAs in skeletal and cardiac muscle development.. DNA Cell Biol 26(4):219-25 PMID: 17465888
- 4. Lui JC et al.. 2011. Mechanisms limiting body growth in mammals.. Endocr Rev 32(3):422-40 PMID: 21441345
- 5. Kubli DA et al.. 2014. Cardiomyocyte health: adapting to metabolic changes through autophagy.. Trends Endocrinol Metab 25(3):156-64 PMID: 24370004
- 6. Song G et al.. 2018. Deletion of Pr72 causes cardiac developmental defects in Zebrafish.. PLoS One 13(11):e0206883 PMID: 30481179
- 7. Lohela M et al.. 2009. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis.. Curr Opin Cell Biol 21(2):154-65 PMID: 19230644
- 8. Alikunju S et al.. 2022. G3bp1 - microRNA-1 axis regulates cardiomyocyte hypertrophy.. Cell Signal 91:110245 PMID: 35017014
