GO:1901724 positive regulation of cell proliferation involved in kidney development: Signaling Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1901724 describes any process that activates or increases the frequency, rate or extent of cell proliferation specifically during kidney development.
• The term is a biological process child of positive regulation of cell proliferation and is restricted to the developmental context of kidney formation.
• Key molecular drivers include p53, Hippo pathway components, HIF2α, β-catenin/FOSL1, and JAK/STAT signaling, all of which influence nephron progenitor expansion or renal epithelial proliferation.
• Dysregulation of this process is linked to renal cell carcinoma, Wilms tumor, and congenital kidney malformations.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to dissect causal roles of candidate genes in kidney developmental proliferation.
• Understanding GO:1901724 supports regenerative nephrology, cancer biology, and developmental toxicity research.
Description
GO:1901724, positive regulation of cell proliferation involved in kidney development, is a Gene Ontology biological process term that captures the upstream signals and molecular events that stimulate cell division during the formation of the kidney. This term is distinct from general cell proliferation because it is spatially and temporally restricted to the developing kidney, where coordinated proliferation of nephron progenitors, ureteric bud cells, and stromal cells is required for proper organ size and function. Researchers studying kidney organogenesis, congenital anomalies of the kidney and urinary tract (CAKUT), and renal cancers rely on this term to annotate genes and pathways that drive proliferative expansion in renal tissues. The term is supported by experimental evidence from model organisms and human cell studies, and it integrates signaling cascades such as Hippo, p53, HIF2α, and JAK/STAT that converge on cell-cycle regulators. Because kidney development is a paradigm for branching morphogenesis and progenitor self-renewal, understanding positive regulation of cell proliferation in this context has broad implications for regenerative medicine and cancer biology.
positive regulation of cell proliferation involved in kidney development At A Glance
| GO ID | GO:1901724 |
|---|---|
| GO term | positive regulation of cell proliferation involved in kidney development |
| Ontology | biological_process |
| Synonym | activation of cell proliferation involved in kidney development; up regulation of cell proliferation involved in kidney development; up-regulation of cell proliferation involved in kidney development; upregulation of cell proliferation involved in kidney development |
| Major function | Stimulates cell division during kidney organogenesis, influencing nephron number and renal size. |
| Related pathways | Hippo signaling, p53 regulation, HIF2α, β-catenin/FOSL1, JAK/STAT. |
| Disease relevance | Renal cell carcinoma, Wilms tumor, congenital kidney malformations. |
| Research methods | CRISPR screens, lineage tracing, single-cell RNA-seq, organoid culture. |
What Is GO:1901724?
According to the QuickGO definition, GO:1901724 refers to any process that activates or increases the frequency, rate or extent of cell proliferation involved in kidney development. In other words, it is the positive regulatory arm of the cell proliferation that occurs specifically as the kidney forms, encompassing signals that promote progenitor expansion, nephron endowment, and renal growth.
Why Is positive regulation of cell proliferation involved in kidney development Important in Cell Biology?
GO:1901724 is important because it defines the regulatory inputs that control how many cells are produced during kidney development, directly impacting nephron number, renal function, and susceptibility to disease. Disruption of this process can lead to congenital anomalies or predispose to renal cancers, making it a key area for developmental and cancer research.
• Determines nephron endowment and kidney size during development.
• Links developmental signaling pathways to cell-cycle control.
• Implicated in renal cell carcinoma progression and therapy resistance.
• Relevant to Wilms tumor and other pediatric kidney cancers.
• Provides targets for regenerative nephrology and organoid engineering.
• Helps interpret single-cell transcriptomics of kidney organogenesis.
• Guides CRISPR screens for kidney developmental regulators.
• Informs toxicity testing for environmental agents affecting kidney development.
• Connects inflammation and cancer stem cell expansion in kidney tumors.
• Supports precision medicine by identifying prognostic biomarkers.
What Happens During positive regulation of cell proliferation involved in kidney development?
Initiation by growth factor and morphogen signaling
In simple terms: Signals from surrounding tissues tell kidney cells to start dividing.
Positive regulation of cell proliferation in kidney development begins with extracellular cues such as Wnt, FGF, and BMP that activate intracellular cascades in nephron progenitors and ureteric bud cells. These signals converge on transcriptional programs that drive cell-cycle entry, and their intensity and duration are tightly controlled to ensure proper kidney architecture.
Integration of Hippo and p53 pathways
In simple terms: Internal safety switches decide whether cells should divide or stop.
The Hippo pathway restricts proliferation by phosphorylating YAP/TAZ, and its inactivation promotes kidney cell proliferation during development and repair. Conversely, p53 acts in a tissue-specific manner to limit progenitor expansion, and its loss can enhance proliferative responses in kidney development. The balance between these pathways determines the extent of positive regulation.
Cell-cycle machinery activation
In simple terms: The cell's engine for division is switched on.
Downstream of these signals, cyclin-dependent kinases and their partners are activated, leading to DNA replication and mitosis. Positive regulation of cell proliferation involved in kidney development ultimately increases the frequency of cells entering S phase and completing division, as evidenced by increased Ki-67 staining and EdU incorporation in developing kidneys.
Feedback and termination
In simple terms: The process is turned off when enough cells are made.
Negative feedback loops, including those mediated by p53 and Hippo signaling, ensure that proliferation ceases appropriately once nephron progenitors differentiate. Dysregulation of these brakes can lead to excessive proliferation, as seen in renal tumors.
Key Genes Involved in GO:1901724 positive regulation of cell proliferation involved in kidney development
The following genes and proteins have been experimentally linked to positive regulation of cell proliferation involved in kidney development, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TP53 | Tissue-specific regulation of proliferation during kidney development | Knockout models reveal enhanced progenitor expansion |
| YAP1 | Hippo pathway effector promoting proliferation | Modulates kidney growth and regeneration |
| HIF2A | Expansion of CXCR4-positive cancer stem-like cells in renal cell carcinoma | Links hypoxia to proliferative signaling |
| CTNNB1 | β-catenin drives FOSL1 expression and proliferation | Oncogenic driver in renal cell carcinoma |
| FOSL1 | Transcription factor downstream of β-catenin | Promotes renal cancer progression |
| JAK2 | JAK/STAT pathway activation in ccRCC | Mediates sunitinib resistance |
| STAT3 | Transcription factor downstream of JAK | Promotes proliferation and survival |
| NUSAP1 | Pan-cancer biomarker associated with proliferation | Predicts prognosis and immunotherapy response |
| CXCR4 | Receptor marking cancer stem-like cells | Expansion driven by HIF2α |
| SCARB1 | Cholesterol metabolism and M2 macrophage polarization | Promotes ccRCC via IGF2BP3 |
| IGF2BP3 | RNA-binding protein stabilizing SCARB1 mRNA | Facilitates M2 polarization in ccRCC |
| CLIP170 | Enhances FOSL1 via β-catenin stabilization | Drives renal cell carcinoma progression |
| SNORA33 | snoRNA promoting ccRCC via JAK/STAT | Potential therapeutic target |
| ABCA1 | Cholesterol efflux transporter; circABCA1 promotes ccRCC | Reprogramming cholesterol metabolism |
How Is positive regulation of cell proliferation involved in kidney development Regulated?
Positive regulation of cell proliferation involved in kidney development is controlled by a network of signaling pathways. The Hippo pathway acts as a brake by phosphorylating YAP/TAZ, and its inactivation increases proliferation. p53 provides tissue-specific restraint, and its loss enhances progenitor expansion. HIF2α promotes the expansion of CXCR4-positive cancer stem-like cells under hypoxia. β-catenin and FOSL1 form a positive feedback loop that drives proliferation in renal cell carcinoma. JAK/STAT signaling, triggered by SNORA33, promotes ccRCC development and drug resistance. Additionally, cholesterol metabolism and macrophage polarization via circABCA1/IGF2BP3/SCARB1 influence the tumor microenvironment and proliferative signals.
positive regulation of cell proliferation involved in kidney development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TP53 | Wilms tumor, renal cell carcinoma | Knockout mouse, point-mutation knock-in |
| HIF2A | Clear cell renal cell carcinoma | Overexpression in RCC cell lines |
| CTNNB1 | Renal cell carcinoma | Knock-in of stabilizing mutation |
| JAK2 | ccRCC with sunitinib resistance | Knockout or point-mutation in ccRCC cells |
| SCARB1 | ccRCC progression | Knockout in ccRCC organoids |
Renal Cell Carcinoma
Dysregulated positive regulation of cell proliferation involved in kidney development contributes to renal cell carcinoma (RCC). β-catenin stabilization by CLIP170 enhances FOSL1 expression, driving RCC progression. HIF2α expands CXCR4-positive cancer stem-like cells, promoting tumor growth. SNORA33 triggers JAK/STAT signaling, leading to sunitinib resistance. CircABCA1 reprograms cholesterol metabolism and facilitates M2 macrophage polarization via IGF2BP3-mediated SCARB1 mRNA stabilization, promoting ccRCC. NUSAP1 is a predictive biomarker for prognosis and immunotherapy response in pan-cancer including RCC.
Wilms Tumor and Pediatric Kidney Cancer
Wilms tumor arises from aberrant proliferation of nephron progenitors. p53 mutations are associated with anaplastic Wilms tumor and poor prognosis, highlighting the role of p53 in restraining proliferation during kidney development. The inflammatory microenvironment may also contribute to kidney cancer progression.
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Disruption of positive regulation of cell proliferation during kidney development can lead to CAKUT, including renal hypoplasia. Hippo pathway dysregulation affects kidney size and nephron number. p53 loss can alter progenitor pool size, potentially causing structural abnormalities.
From positive regulation of cell proliferation involved in kidney development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X promote proliferation during kidney development? | CRISPR knockout in mouse kidney organoids |
| Does a point mutation in gene Y alter proliferative signaling? | Knock-in of point mutation in cell lines |
| Does overexpression of gene Z drive renal cancer? | Overexpression in RCC cell lines or xenografts |
| What is the role of a non-coding RNA in proliferation? | Knockout or overexpression of snoRNA/miRNA |
| How does a gene affect stem-like cell expansion? | Lineage tracing and CXCR4 reporter |
| Can a candidate gene be targeted therapeutically? | Conditional knockout and drug treatment |
How to Study the positive regulation of cell proliferation involved in kidney development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene essentiality for proliferation | Identify positive regulators in kidney organoids |
| EdU incorporation | DNA synthesis | Quantify proliferation in developing kidneys |
| Single-cell RNA-seq | Transcriptional states | Discover progenitor subpopulations |
| Lineage tracing | Cell fate and expansion | Track nephron progenitors in vivo |
| Phosphoproteomics | Signaling pathway activity | Assess Hippo/JAK/STAT changes |
| Organoid culture | 3D growth and differentiation | Model kidney development and disease |
| Xenograft assays | Tumor growth | Test oncogenic potential of candidate genes |
| Immunohistochemistry | Protein expression and localization | Validate markers in patient samples |
CRISPR Screens for Proliferation Regulators
Genome-wide CRISPR knockout or activation screens in kidney organoids or renal cell lines can identify genes that positively regulate proliferation during kidney development. Hits are validated by measuring EdU incorporation or Ki-67 staining.
Single-Cell RNA Sequencing
scRNA-seq of developing kidneys reveals transcriptional heterogeneity and identifies proliferating progenitor populations. This method can pinpoint genes co-expressed with cell-cycle markers.
Lineage Tracing and Imaging
Genetic lineage tracing in mice, combined with confocal imaging of markers like Six2 and Ki-67, visualizes proliferative expansion of nephron progenitors in situ.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics can quantify changes in signaling pathways (e.g., Hippo, JAK/STAT) upon genetic perturbation, linking molecular events to proliferative outcomes.
How CRISPR Can Be Used to Study GO:1901724 positive regulation of cell proliferation involved in kidney development
Knockout
CRISPR knockout of candidate genes in kidney organoids or cell lines can determine whether they are required for positive regulation of cell proliferation involved in kidney development. For example, knocking out TP53 enhances progenitor expansion, while knocking out JAK2 reduces ccRCC proliferation.
Point Mutation
Introducing specific point mutations (e.g., in CTNNB1 or TP53) via CRISPR base editing or HDR allows researchers to study the effects of clinically relevant mutations on proliferative signaling.
Knock-in
Knock-in of reporter genes (e.g., fluorescent proteins) or epitope tags at endogenous loci enables real-time tracking of proliferation and protein localization in developing kidneys.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of genes such as HIF2A or SNORA33 can model gain-of-function states and assess their impact on kidney cell proliferation and tumorigenesis.
How EDITGENE Supports positive regulation of cell proliferation involved in kidney development Research
Researchers studying positive regulation of cell proliferation involved in kidney development-related genes often need to determine whether a candidate gene is causally involved in proliferative control or merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR services to enable such causal studies.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of cell proliferation involved in kidney development research.
Frequently Asked Questions About positive regulation of cell proliferation involved in kidney development
What is GO:1901724?
GO:1901724 is a Gene Ontology biological process term defined as any process that activates or increases the frequency, rate or extent of cell proliferation involved in kidney development.
What genes are involved in positive regulation of cell proliferation involved in kidney development?
Key genes include TP53, YAP1, HIF2A, CTNNB1, FOSL1, JAK2, STAT3, NUSAP1, CXCR4, SCARB1, IGF2BP3, CLIP170, SNORA33, and ABCA1.
How is cell proliferation regulated during kidney development?
It is regulated by signaling pathways such as Hippo, p53, HIF2α, β-catenin/FOSL1, and JAK/STAT, which control cell-cycle entry and progenitor expansion.
What diseases are associated with dysregulation of this process?
Renal cell carcinoma, Wilms tumor, and congenital anomalies of the kidney and urinary tract (CAKUT) are associated with dysregulation.
What research methods are used to study GO:1901724?
CRISPR screens, single-cell RNA-seq, lineage tracing, organoid culture, proteomics, and imaging are commonly used.
How can CRISPR help study kidney developmental proliferation?
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of candidate genes in kidney cells and organoids.
What is the role of p53 in kidney development?
p53 acts in a tissue-specific manner to restrain progenitor proliferation during kidney development, and its loss enhances expansion.
How does HIF2α contribute to kidney cancer?
HIF2α promotes the expansion of CXCR4-positive cancer stem-like cells in renal cell carcinoma.
What is the Hippo pathway's role in kidney development?
The Hippo pathway restricts proliferation by inhibiting YAP/TAZ; its dysregulation affects kidney size and repair.
Can EDITGENE provide custom models for kidney development research?
Yes, EDITGENE offers knockout, point mutation, knock-in, overexpression, and CRISPR screening services tailored to kidney development and disease.
Conclusion
GO:1901724, positive regulation of cell proliferation involved in kidney development, is a critical biological process that integrates developmental signals to control nephron progenitor expansion and kidney growth. Its dysregulation is linked to renal cell carcinoma, Wilms tumor, and congenital kidney anomalies. Understanding the molecular players and regulatory mechanisms offers opportunities for therapeutic intervention and regenerative medicine. EDITGENE provides the CRISPR tools and bioinformatics expertise to dissect this process and accelerate translational research.
References
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- 2. 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
- 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. Huang Y et al.. 2024. CLIP170 enhancing FOSL1 expression via attenuating ubiquitin-mediated degradation of β-catenin drives renal cell carcinoma progression.. Cell Mol Life Sci 81(1):467 PMID: 39607512
- 5. Sun Y et al.. 2022. The critical role of the Hippo signaling pathway in kidney diseases.. Front Pharmacol 13:988175 PMID: 36483738
- 6. Saifudeen Z. 2017. Tissue-Specific Functions of p53 During Kidney Development.. Results Probl Cell Differ 60:111-136 PMID: 28409344
- 7. Sun J et al.. 2025. SNORA33 Promotes Clear Cell Renal Cell Carcinoma Development and Resistance to Sunitinib Through Triggering the JAK/STAT Pathway.. IUBMB Life 77(9):e70058 PMID: 40990946
- 8. Micucci C et al.. 2015. HIF2α is involved in the expansion of CXCR4-positive cancer stem-like cells in renal cell carcinoma.. Br J Cancer 113(8):1178-85 PMID: 26439684
