GO:1901723 negative regulation of cell proliferation involved in kidney development: Regulatory Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1901723 describes any process that stops, prevents, or reduces the frequency, rate, or extent of cell proliferation specifically during kidney development.
• This biological process is essential for proper nephron endowment and kidney size, and its dysregulation is linked to renal cell carcinoma, polycystic kidney disease, and other renal pathologies.
• Key molecular players include Nrf2, PTEN, PI3K/AKT, FGF signaling, and apoptosis regulators, which collectively restrain excessive proliferation in the developing kidney.
• Loss of negative regulation can lead to hyperproliferative disorders such as Wilms tumor and renal cell carcinoma, making this process a target for therapeutic intervention.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable precise dissection of genes controlling this process.
• Understanding GO:1901723 provides insights into kidney development, regeneration, and cancer, with implications for biomarker discovery and targeted therapy.
Description
The Gene Ontology term GO:1901723, negative regulation of cell proliferation involved in kidney development, defines any process that stops, prevents, or reduces the frequency, rate, or extent of cell proliferation specifically during kidney development. This biological process is critical for ensuring correct nephron number and kidney architecture, as unchecked proliferation can lead to developmental abnormalities and renal disease. Research into this term has revealed a complex interplay of signaling pathways, transcription factors, and cell cycle regulators that collectively restrain cell division in the developing kidney. Dysregulation of this process is implicated in a spectrum of kidney disorders, including renal cell carcinoma, polycystic kidney disease, and congenital anomalies of the kidney and urinary tract. For researchers, understanding the molecular mechanisms underlying GO:1901723 offers opportunities to identify therapeutic targets and biomarkers for renal diseases. Moreover, the advent of CRISPR gene editing has enabled precise functional studies of genes involved in this process, accelerating the translation of basic findings into clinical applications. This article synthesizes current knowledge on GO:1901723, covering its definition, key genes, regulatory mechanisms, disease associations, and state-of-the-art research methods. By focusing on verified literature, we provide a comprehensive resource for scientists investigating kidney development and related pathologies.
negative regulation of cell proliferation involved in kidney development At A Glance
| GO ID | GO:1901723 |
|---|---|
| GO term | negative regulation of cell proliferation involved in kidney development |
| Ontology | biological_process |
| Synonym | down regulation of cell proliferation involved in kidney development, down-regulation of cell proliferation involved in kidney development, downregulation of cell proliferation involved in kidney development, inhibition of cell proliferation involved in kidney development |
| Major function | Stops, prevents, or reduces the frequency, rate, or extent of cell proliferation during kidney development |
| Related processes | Kidney development, cell proliferation, negative regulation of cell population proliferation |
| Disease relevance | Renal cell carcinoma, polycystic kidney disease, Wilms tumor, congenital kidney anomalies |
| Key regulators | Nrf2, PTEN, PI3K/AKT, FGF signaling, apoptosis regulators |
What Is GO:1901723?
GO:1901723 is a biological process term that encompasses any mechanism that negatively regulates cell proliferation during kidney development. In other words, it includes all molecular events that slow down, halt, or prevent the division of cells that contribute to the formation of the kidney. This regulation is essential for balancing cell growth and differentiation, ensuring proper organ size and function.
Why Is negative regulation of cell proliferation involved in kidney development Important in Cell Biology?
GO:1901723 is crucial because it ensures proper kidney development by preventing excessive cell proliferation, which could otherwise lead to tumorigenesis or structural abnormalities. Disruption of this process is associated with renal cell carcinoma, polycystic kidney disease, and other renal disorders, making it a focal point for understanding kidney pathology and developing targeted therapies.
• Maintains correct nephron number and kidney size during development.
• Prevents hyperproliferative diseases such as Wilms tumor and renal cell carcinoma.
• Involved in the pathogenesis of polycystic kidney disease through dysregulated apoptosis and proliferation.
• Modulated by key signaling pathways including PI3K/PTEN/AKT and Nrf2, which are therapeutic targets.
• Provides biomarkers for cancer prognosis and immunotherapy response, e.g., NUSAP1 and ANKRD52.
• Essential for kidney regeneration and repair processes.
• Offers insights into developmental origins of adult kidney diseases.
• Enables CRISPR-based functional genomics to identify novel regulators.
• Links inflammation and cancer through NF-kB and Nrf2 crosstalk.
• Guides development of targeted therapies for renal malignancies.
What Happens During negative regulation of cell proliferation involved in kidney development?
Initiation of Negative Regulation
In simple terms: The process begins when signals tell kidney cells to stop dividing.
Negative regulation of cell proliferation in kidney development is initiated by extracellular cues such as FGF signaling, which can inhibit proliferation through the FGF metabolic axis. Additionally, activation of the Nrf2 pathway has been shown to promote wound healing and may restrain excessive proliferation in renal cells. These signals converge on cell cycle regulators to halt progression.
Cell Cycle Arrest
In simple terms: Cells are paused in the cell cycle, preventing them from dividing.
Key molecular brakes include the PTEN tumor suppressor, which antagonizes PI3K/AKT signaling, leading to cell cycle arrest. Loss of PTEN results in unchecked proliferation, highlighting its role in negative regulation. Similarly, apoptosis regulators can indirectly limit proliferation by eliminating excess cells.
Apoptosis and Clearance
In simple terms: Excess cells are programmed to die, reducing overall proliferation.
Apoptosis plays a critical role in negative regulation of cell proliferation during kidney development by removing superfluous cells. In polycystic kidney disease, dysregulated apoptosis contributes to cyst formation, underscoring the balance between proliferation and cell death.
Integration with Differentiation
In simple terms: Stopping division allows cells to mature into specialized kidney cells.
Negative regulation of proliferation is tightly coupled with cellular differentiation. For example, Nrf2 signaling not only modulates proliferation but also promotes cytoprotective gene expression, facilitating differentiation. This integration ensures proper nephron formation.
Feedback and Termination
In simple terms: Once enough cells are made, the stop signals are reinforced.
Feedback loops involving inflammatory mediators and growth factors help terminate proliferation. Chronic inflammation, as seen in kidney cancer, can override these brakes, leading to sustained proliferation. Thus, negative regulation must be robust to prevent oncogenesis.
Key Genes Involved in GO:1901723 negative regulation of cell proliferation involved in kidney development
The following genes and proteins are key players in the negative regulation of cell proliferation involved in kidney development, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| NUSAP1 | Microtubule assembly, cell proliferation | Biomarker for prognosis and immunotherapy response in pan-cancer, including kidney |
| FGF | Signaling in development and metabolism | Regulates proliferation in kidney development via FGF metabolic axis |
| NF-kB | Inflammation and cancer | Links inflammation to kidney cancer progression |
| Nrf2 | Antioxidant response, cytoprotection | Modulates proliferation and wound healing; therapeutic target in RCC |
| ANKRD52 | Unknown, potential tumor suppressor | Clinical and immunological significance in pan-cancer |
| PTEN | Tumor suppressor, PI3K/AKT inhibitor | Frequently mutated in renal cell carcinoma; regulates proliferation |
| PI3K | Lipid kinase, promotes proliferation | Oncogenic driver in RCC; target of negative regulation |
| AKT | Serine/threonine kinase, survival | Mediates PI3K signaling; inhibition reduces proliferation |
| Bcl-2 | Anti-apoptotic | Dysregulated in polycystic kidney disease |
| Bax | Pro-apoptotic | Promotes apoptosis, limiting proliferation |
| Caspase-3 | Executioner of apoptosis | Mediates cell death in kidney development |
| mTOR | Growth and proliferation | Integrates signals to regulate cell growth |
| Wnt | Developmental signaling | Controls nephron progenitor proliferation |
| p53 | Tumor suppressor | Induces cell cycle arrest and apoptosis |
| p21 | CDK inhibitor | Mediates cell cycle arrest downstream of p53 |
| p27 | CDK inhibitor | Regulates proliferation in kidney development |
| c-Myc | Transcription factor, proliferation | Overexpressed in many cancers; target of negative regulation |
| Cyclin D1 | Cell cycle progression | Promotes G1/S transition; inhibited by negative regulators |
How Is negative regulation of cell proliferation involved in kidney development Regulated?
The negative regulation of cell proliferation involved in kidney development is controlled by a network of signaling pathways and transcription factors. The PI3K/PTEN/AKT pathway is central: PTEN acts as a brake by dephosphorylating PIP3, thereby inhibiting AKT and downstream proliferative signals. Nrf2 activation can also inhibit proliferation while promoting cytoprotection, and its pharmacological activation has been shown to promote wound healing. FGF signaling modulates proliferation through the FGF metabolic axis, which can either promote or inhibit proliferation depending on context. Additionally, apoptosis regulators such as Bcl-2 and Bax influence cell number by controlling cell death. Inflammatory pathways involving NF-kB can override these brakes, leading to hyperproliferation in kidney cancer. Thus, the process is regulated at multiple levels, ensuring tight control of cell numbers during kidney development.
negative regulation of cell proliferation involved in kidney development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PTEN | Renal cell carcinoma, Cowden syndrome | PTEN knockout mouse, RCC cell lines |
| Nrf2 | Renal cell carcinoma, wound healing | Nrf2 knockout/overexpression models |
| NUSAP1 | Pan-cancer prognosis, immunotherapy response | CRISPR knockout in RCC cell lines |
| ANKRD52 | Pan-cancer clinical significance | Knockout and overexpression in kidney cells |
| Bcl-2 | Polycystic kidney disease | Bcl-2 transgenic mice, PKD models |
Renal Cell Carcinoma
Dysregulation of negative regulation of cell proliferation is a hallmark of renal cell carcinoma (RCC). Loss of PTEN or activation of PI3K/AKT signaling leads to unchecked proliferation. Nrf2 signaling, which normally restrains proliferation, is often altered in RCC, and its pharmacological activation is being explored as a therapeutic strategy. Inflammatory pathways involving NF-kB further promote tumorigenesis. Biomarkers such as NUSAP1 and ANKRD52 have been identified as prognostic and immunotherapeutic response predictors in pan-cancer analyses including RCC.
Polycystic Kidney Disease
Polycystic kidney disease (PKD) is characterized by abnormal proliferation of cyst-lining epithelial cells. Apoptosis is dysregulated in PKD, contributing to cyst growth. The balance between proliferation and apoptosis is disrupted, leading to progressive cyst formation. Negative regulators of proliferation, such as p53 and CDK inhibitors, are often impaired in PKD, suggesting that restoring these brakes could be therapeutic.
Wilms Tumor and Congenital Anomalies
Wilms tumor, a pediatric kidney cancer, arises from aberrant proliferation of nephron progenitors. Defects in negative regulation of proliferation during kidney development can lead to persistent progenitor pools and tumor formation. Congenital anomalies of the kidney and urinary tract (CAKUT) may also result from disrupted proliferation control, highlighting the importance of this process in developmental biology.
From negative regulation of cell proliferation involved in kidney development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate proliferation in kidney development? | CRISPR knockout in kidney organoids or mouse models |
| What is the effect of a point mutation in gene Y on proliferation? | CRISPR point mutation knock-in in cell lines |
| How does overexpression of gene Z affect nephron number? | CRISPR-mediated overexpression in zebrafish or mouse |
| Which genes are essential for negative regulation? | Genome-wide CRISPR library screening in kidney progenitor cells |
| What are the downstream targets of Nrf2 in kidney development? | ChIP-seq and RNA-seq after Nrf2 knockout/overexpression |
| Can we model PKD with CRISPR-edited organoids? | Knockout of PKD1/PKD2 in human kidney organoids |
How to Study the negative regulation of cell proliferation involved in kidney development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Gene essentiality and proliferation effects | Identify negative regulators in kidney cells |
| RNA-seq | Transcriptional changes | Compare proliferating vs. quiescent kidney cells |
| Proteomics | Protein expression and modifications | Discover signaling changes in PI3K/AKT |
| EdU incorporation | DNA synthesis (proliferation) | Quantify proliferation in organoids |
| Annexin V staining | Apoptosis | Measure cell death in PKD models |
| Live-cell imaging | Real-time proliferation dynamics | Track nephron progenitor divisions |
| ChIP-seq | Transcription factor binding | Map Nrf2 or p53 targets in kidney development |
CRISPR Screening
Genome-wide CRISPR knockout or activation screens can identify novel regulators of negative proliferation in kidney development. These screens use pooled sgRNA libraries to perturb thousands of genes and select for changes in proliferation rates, followed by next-generation sequencing to identify enriched or depleted sgRNAs.
Transcriptomics and Proteomics
RNA-seq and proteomics can reveal gene expression changes associated with negative regulation. For example, comparing proliferating versus quiescent kidney cells can identify upregulated tumor suppressors and cell cycle inhibitors. Phosphoproteomics can uncover signaling changes in PI3K/AKT pathways.
Imaging and Lineage Tracing
Live-cell imaging and lineage tracing in model organisms (e.g., zebrafish, mouse) allow visualization of proliferation dynamics during kidney development. Fluorescent reporters for cell cycle phases or apoptosis can quantify negative regulation in real time.
Functional Assays
Proliferation assays (e.g., EdU incorporation, MTT) and apoptosis assays (e.g., Annexin V, caspase activity) are used to measure the effects of gene perturbations. These are often combined with CRISPR editing to validate candidate genes.
How CRISPR Can Be Used to Study GO:1901723 negative regulation of cell proliferation involved in kidney development
Knockout
CRISPR knockout (KO) is used to completely abolish gene function and assess its role in negative regulation of proliferation. For example, KO of PTEN in kidney cells leads to increased proliferation, confirming its role as a negative regulator. KO models can be generated in cell lines, organoids, or mice to study developmental and disease phenotypes.
Point Mutation
CRISPR point mutation knock-in introduces specific amino acid changes to study structure-function relationships or mimic disease-associated mutations. For instance, mutating phosphorylation sites in AKT can reveal their importance in proliferation control. This approach is valuable for dissecting signaling pathways with precision.
Knock-in
Knock-in of reporter genes (e.g., fluorescent proteins) or tags allows visualization and tracking of proteins involved in negative regulation. Tagged knock-in of cell cycle inhibitors can reveal their localization and dynamics during kidney development. This technique also enables conditional alleles for spatial-temporal control.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression can elevate gene expression to study gain-of-function effects. Overexpressing negative regulators such as PTEN or Nrf2 can suppress proliferation and reduce tumor growth in models of RCC. This approach helps validate therapeutic targets.
How EDITGENE Supports negative regulation of cell proliferation involved in kidney development Research
Researchers studying negative regulation of cell proliferation involved in kidney development-related genes often need to determine whether a candidate gene is causally involved in restraining proliferation or whether its manipulation alters disease phenotypes. EDITGENE provides a comprehensive suite of CRISPR services to enable such functional studies with high precision and efficiency.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of cell proliferation involved in kidney development research.
Frequently Asked Questions About negative regulation of cell proliferation involved in kidney development
What is GO:1901723?
GO:1901723 is a Gene Ontology term for any process that stops, prevents, or reduces the frequency, rate, or extent of cell proliferation involved in kidney development.
What genes are involved in negative regulation of cell proliferation in kidney development?
Key genes include PTEN, Nrf2, NUSAP1, ANKRD52, FGF, and apoptosis regulators like Bcl-2 and Bax.
How is negative regulation of cell proliferation in kidney development studied?
Researchers use CRISPR knockout, RNA-seq, proteomics, imaging, and functional assays to study this process.
Why is negative regulation of cell proliferation important in kidney development?
It ensures proper nephron number and prevents hyperproliferative diseases such as renal cell carcinoma and polycystic kidney disease.
What diseases are associated with dysregulation of GO:1901723?
Renal cell carcinoma, polycystic kidney disease, Wilms tumor, and congenital kidney anomalies are linked to disrupted negative regulation.
What signaling pathways control negative regulation of proliferation in kidney development?
The PI3K/PTEN/AKT, Nrf2, FGF, and apoptosis pathways are major regulators.
Can CRISPR be used to study GO:1901723?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable precise functional studies of genes involved in this process.
What is the role of Nrf2 in kidney development?
Nrf2 modulates proliferation and cytoprotection; its activation promotes wound healing and may restrain excessive proliferation.
How does PTEN regulate cell proliferation in the kidney?
PTEN inhibits PI3K/AKT signaling, leading to cell cycle arrest and reduced proliferation; its loss is common in renal cell carcinoma.
What are potential therapeutic targets for diseases linked to GO:1901723?
PTEN, PI3K/AKT, Nrf2, and NUSAP1 are promising targets for drug development and immunotherapy.
Conclusion
GO:1901723, negative regulation of cell proliferation involved in kidney development, is a fundamental biological process that safeguards proper kidney formation and function. Its dysregulation contributes to a range of renal diseases, including cancer and cystic disorders. Through advanced CRISPR technologies and multi-omics approaches, researchers can now dissect the intricate regulatory networks controlling this process, paving the way for novel diagnostics and therapeutics. EDITGENE stands ready to support these efforts with tailored gene editing and screening services.
References
- 1. Zheng H et al.. 2023. Comprehensive pan-cancer analysis reveals NUSAP1 is a novel predictive biomarker for prognosis and immunotherapy response.. Int J Biol Sci 19(14):4689-4708 PMID: 37781040
- 2. Li X. 2019. The FGF metabolic axis.. Front Med 13(5):511-530 PMID: 31495905
- 3. de Vivar Chevez AR et al.. 2014. The role of inflammation in kidney cancer.. Adv Exp Med Biol 816:197-234 PMID: 24818725
- 4. Schiavoni V et al.. 2024. Nrf2 Signaling in Renal Cell Carcinoma: A Potential Candidate for the Development of Novel Therapeutic Strategies.. Int J Mol Sci 25(24) PMID: 39769005
- 5. Yin HZ et al.. 2024. Clinical and Immunological Significance of ANKRD52 in Pan-Cancer.. Biochem Genet 62(6):4335-4358 PMID: 38296907
- 6. Victor P et al.. 2020. Pharmacological activation of Nrf2 promotes wound healing.. Eur J Pharmacol 886:173395 PMID: 32710954
- 7. Fang Y et al.. 2022. Research Progress of PI3K/PTEN/AKT Signaling Pathway Associated with Renal Cell Carcinoma.. Dis Markers 2022:1195875 PMID: 36046376
- 8. Li X et al.. 2015. Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment.. PMID: 27512777
