GO:0035799 ureter maturation: Developmental Process, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035799 ureter maturation is a developmental process, independent of morphogenetic shape change, that is required for the ureter to attain its fully functional state.
• Maturation of the ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases, including PTPRF (LAR).
• Ureter myogenesis involves transcriptional regulators such as Teashirt (TSHZ) and is essential for formation of the muscular tube that transports urine.
• DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis.
• Congenital anomalies of the kidney and urinary tract (CAKUT) frequently arise from defective ureter development and maturation.
• Research on ureter maturation uses mouse models, organoid tubules, and imaging to study Ca2+ signaling dynamics in maturing ureteric bud- and collecting duct-derived tubules.
Description
Ureter maturation (GO:0035799) is defined as a developmental process, independent of morphogenetic (shape) change, that is required for the ureter to attain its fully functional state. The ureter is a muscular tube that transports urine from the kidney to the urinary bladder or from the Malpighian tubule to the hindgut. This process is critical for establishing a patent and functional urinary tract, and its disruption leads to congenital anomalies of the kidney and urinary tract (CAKUT). Understanding ureter maturation is therefore essential for researchers studying renal development, congenital disease, and tissue engineering. The process involves coordinated signaling, transcriptional regulation, and cell-cell interactions that ensure the ureter connects properly to the bladder and develops a functional muscular wall [2,4,7]. Recent studies have begun to unravel the molecular players, including receptor tyrosine phosphatases, transcription factors, and retinoic acid signaling, that orchestrate this maturation [2,7]. This article synthesizes current knowledge based on authoritative QuickGO data and published literature to provide a research-grade overview of ureter maturation.
ureter maturation At A Glance
| GO ID | GO:0035799 |
|---|---|
| GO term | ureter maturation |
| Ontology | biological_process |
| Synonym | None |
| Definition | A developmental process, independent of morphogenetic (shape) change, that is required for the ureter to attain its fully functional state. The ureter is a muscular tube that transports urine from the kidney to the urinary bladder or from the Malpighian tubule to the hindgut. |
| Major function | Functional maturation of the ureter for urine transport |
| Related processes | Ureter development, ureter-bladder connection, ureter myogenesis |
| Key regulators | LAR family receptor protein tyrosine phosphatases, Teashirt, DLG1, retinoic acid signaling, Ret |
| Associated anomalies | Congenital anomalies of the kidney and urinary tract (CAKUT) |
What Is GO:0035799?
According to the Gene Ontology, ureter maturation (GO:0035799) is a biological process defined as a developmental process, independent of morphogenetic (shape) change, that is required for the ureter to attain its fully functional state. The ureter is a muscular tube that transports urine from the kidney to the urinary bladder or from the Malpighian tubule to the hindgut. This term captures the functional maturation steps that occur after the basic shape of the ureter is established, including differentiation of cell types, establishment of proper connections, and acquisition of contractile and transport functions [1,2,4].
Why Is ureter maturation Important in Cell Biology?
Ureter maturation is essential for normal urinary function, and defects in this process lead to congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common birth defects in humans. Proper maturation ensures that the ureter connects correctly to the bladder and develops a functional muscular wall capable of peristalsis, preventing urine reflux and obstruction [2,4]. Research into ureter maturation provides insights into fundamental developmental mechanisms, including cell-cell signaling, transcriptional regulation, and apoptosis, and informs strategies for tissue engineering and regenerative medicine [1,7].
• Ureter maturation is required for establishing a functional urinary tract and preventing urine reflux.
• Defects in ureter maturation cause congenital anomalies of the kidney and urinary tract (CAKUT).
• LAR family receptor protein tyrosine phosphatases control maturation of the ureter-bladder connection in mice.
• Teashirt (TSHZ) transcription factors regulate ureter myogenesis, essential for peristalsis.
• DLG1 influences distal ureter maturation through retinoic acid signaling, Ret expression, and apoptosis.
• Ca2+ signaling dynamics are important in maturing ureteric bud- and collecting duct-derived tubules.
• Understanding ureter maturation aids in diagnosing and modeling congenital urinary tract defects.
• Mouse models are invaluable for studying ureter maturation due to conserved developmental mechanisms [2,7].
• Organoid systems provide new opportunities to study human ureter maturation in vitro.
• Research on ureter maturation intersects with kidney development, bladder development, and reproductive tract development.
What Happens During ureter maturation?
Establishment of the ureter-bladder connection
In simple terms: The ureter must join the bladder correctly so urine can flow without leaking or backing up.
Maturation of the ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases, including PTPRF (LAR). This process involves precise cell rearrangements and apoptosis to create a patent connection between the distal ureter and the bladder epithelium. Defects in this connection lead to hydronephrosis and other urinary tract anomalies.
Ureter myogenesis and smooth muscle differentiation
In simple terms: The ureter develops a muscular wall that can squeeze urine down to the bladder.
Ureter myogenesis is the process by which mesenchymal cells differentiate into smooth muscle cells that form the muscular wall of the ureter. This process is regulated by transcription factors such as Teashirt (TSHZ) and is essential for peristaltic movement of urine. The muscular tube of the ureter must attain its fully functional state, which includes proper contractile properties.
Role of retinoic acid signaling and DLG1
In simple terms: A signaling molecule called retinoic acid helps guide the final steps of ureter maturation.
DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis. This indicates that retinoic acid signaling and the Ret receptor tyrosine kinase are critical for the maturation of the distal ureter. Disruption of these pathways leads to defective ureter maturation and congenital anomalies.
Calcium signaling dynamics in maturing tubules
In simple terms: Calcium signals inside cells help the ureter and collecting duct mature properly.
Ca2+ signal dynamics in maturing ureteric bud- and collecting duct-derived organoid tubules have been studied, revealing that calcium signaling plays a role in the functional maturation of these tubular structures. These dynamics may regulate cell differentiation, proliferation, and apoptosis during maturation.
Apoptosis and tissue remodeling
In simple terms: Some cells must die in a controlled way to shape the ureter and connect it to the bladder.
Apoptosis is a key mechanism in ureter maturation, particularly in the distal ureter where it facilitates the connection to the bladder [2,7]. Reduced apoptosis due to altered retinoic acid signaling and Ret expression leads to defective maturation. This programmed cell death is independent of morphogenetic shape change and is required for the ureter to attain its fully functional state.
Key Genes Involved in GO:0035799 ureter maturation
The following genes and proteins have been implicated in ureter maturation based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PTPRF (LAR) | Receptor protein tyrosine phosphatase controlling ureter-bladder connection | Mouse knockout studies show defects in ureter maturation |
| PTPRS | LAR family receptor protein tyrosine phosphatase | Potential role in ureter-bladder connection |
| TSHZ2 | Transcription factor regulating ureter myogenesis | Implicated in smooth muscle differentiation |
| TSHZ3 | Transcription factor regulating ureter myogenesis | Implicated in smooth muscle differentiation |
| DLG1 | Scaffolding protein influencing distal ureter maturation | Regulates retinoic acid signaling, Ret expression, apoptosis |
| RET | Receptor tyrosine kinase | Downstream of DLG1, affects ureter maturation |
| ALDH1A2 | Retinoic acid synthesis enzyme | Affects retinoic acid signaling in ureter maturation |
| BMP4 | Signaling molecule | May influence ureter development |
| SHH | Signaling molecule | May influence ureter development |
| WNT5A | Signaling molecule | May influence ureter development |
| FGF8 | Signaling molecule | May influence ureter development |
| SIX1 | Transcription factor | Associated with CAKUT |
| PAX2 | Transcription factor | Associated with CAKUT |
| EYA1 | Transcription factor | Associated with CAKUT |
| SALL1 | Transcription factor | Associated with CAKUT |
| GATA3 | Transcription factor | Associated with CAKUT |
| HNF1B | Transcription factor | Associated with CAKUT |
How Is ureter maturation Regulated?
Ureter maturation is regulated by a complex interplay of signaling pathways and transcription factors. LAR family receptor protein tyrosine phosphatases control the maturation of the ureter-bladder connection. Retinoic acid signaling, acting through DLG1 and Ret, regulates distal ureter maturation and apoptosis. Teashirt transcription factors regulate ureter myogenesis. Calcium signaling dynamics also play a role in the maturation of ureteric bud- and collecting duct-derived tubules. These regulatory mechanisms ensure that the ureter attains its fully functional state.
ureter maturation and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PTPRF | Vesicoureteral reflux, hydronephrosis | Knockout mouse |
| DLG1 | Distal ureter maturation defects | Knockout mouse |
| RET | CAKUT, Hirschsprung disease | Knockout mouse |
| SIX1 | CAKUT | Knockout mouse |
| PAX2 | CAKUT | Knockout mouse |
Congenital anomalies of the kidney and urinary tract (CAKUT)
Defects in ureter maturation are a major cause of congenital anomalies of the kidney and urinary tract (CAKUT), which include hydronephrosis, ureteropelvic junction obstruction, and vesicoureteral reflux. Mutations in genes such as SIX1, PAX2, EYA1, SALL1, GATA3, and HNF1B have been associated with CAKUT, highlighting the importance of proper ureter maturation.
Retroperitoneal fibrosis
Retroperitoneal fibrosis is a condition that can affect the ureter, leading to obstruction and renal failure. While not directly caused by defective ureter maturation, it underscores the clinical importance of a functional ureter.
Ureter-bladder connection defects
Failure of the ureter-bladder connection to mature properly can result in vesicoureteral reflux, where urine flows backward from the bladder to the kidney, leading to infections and kidney damage. Mouse models with mutations in LAR family phosphatases exhibit such defects.
From ureter maturation-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Role of PTPRF in ureter-bladder connection | PTPRF knockout mouse |
| Function of DLG1 in distal ureter maturation | DLG1 knockout mouse |
| Teashirt in ureter myogenesis | TSHZ2/TSHZ3 knockout mouse |
| Calcium signaling in maturing tubules | Organoid tubules from ureteric bud |
| Retinoic acid signaling in ureter maturation | Retinoic acid receptor knockout mouse |
| Apoptosis in ureter maturation | Caspase knockout mouse [2,7] |
How to Study the ureter maturation Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Knockout mouse | Gene function in vivo | Studying PTPRF in ureter-bladder connection |
| Organoid culture | Cellular signaling dynamics | Ca2+ signaling in maturing tubules |
| Live-cell imaging | Cell behavior and apoptosis | Visualizing ureter maturation [2,7] |
| RNA-seq | Transcriptional changes | Identifying genes in ureter myogenesis |
| Proteomics | Protein expression and interactions | Discovering regulators of maturation |
| Lineage tracing | Cell fate and migration | Tracking smooth muscle precursors |
| Immunohistochemistry | Protein localization | Validating gene expression patterns |
| Electron microscopy | Ultrastructure | Examining ureter morphology |
Genetically engineered mouse models
Knockout and conditional knockout mice are widely used to study ureter maturation, as they allow researchers to dissect the role of specific genes in vivo [2,7]. For example, PTPRF and DLG1 knockout mice exhibit defects in ureter-bladder connection and distal ureter maturation, respectively [2,7].
Organoid culture
Organoid tubules derived from ureteric bud and collecting duct can be used to study Ca2+ signal dynamics during maturation in vitro. This system provides a reductionist approach to investigate cellular behaviors and signaling pathways.
Imaging and lineage tracing
Advanced imaging techniques, including live-cell imaging and lineage tracing, allow visualization of ureter maturation processes such as apoptosis, cell migration, and smooth muscle differentiation [2,7]. These methods are essential for understanding the spatiotemporal dynamics of maturation.
Transcriptomics and proteomics
RNA sequencing and proteomics can identify gene expression changes and protein interactions during ureter maturation [1,4]. These approaches help uncover novel regulators and pathways involved in the process [1,4].
How CRISPR Can Be Used to Study GO:0035799 ureter maturation
Knockout
CRISPR knockout can be used to disrupt genes such as PTPRF, DLG1, or TSHZ2 in cell lines or mouse models to study their role in ureter maturation [2,4,7]. This approach enables the generation of isogenic models to dissect gene function.
Point Mutation
Point mutations identified in CAKUT patients (e.g., in SIX1, PAX2) can be introduced using CRISPR to model human disease and study the impact on ureter maturation. This allows precise genotype-phenotype correlation.
Knock-in
Knock-in of reporter genes (e.g., GFP) or tags into endogenous loci can be used to track the expression and localization of proteins involved in ureter maturation, such as RET or DLG1. This facilitates live imaging and biochemical studies.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression can be used to study the effects of increased gene dosage of factors like retinoic acid signaling components on ureter maturation. This helps determine whether excess signaling disrupts normal development.
How EDITGENE Supports ureter maturation Research
Researchers studying ureter maturation-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR-based services to enable functional studies of genes implicated in ureter maturation, from knockout to precise point mutations and knock-in reporters.
Contact EDITGENE today to design your custom CRISPR model for ureter maturation research.
Frequently Asked Questions About ureter maturation
What is ureter maturation?
Ureter maturation (GO:0035799) is a developmental process, independent of morphogenetic shape change, that is required for the ureter to attain its fully functional state.
What genes are involved in ureter maturation?
Key genes include PTPRF, PTPRS, TSHZ2, TSHZ3, DLG1, RET, and ALDH1A2, among others [2,4,7].
What is the role of LAR family phosphatases in ureter maturation?
LAR family receptor protein tyrosine phosphatases, such as PTPRF, control the maturation of the ureter-bladder connection in mice.
How does DLG1 affect ureter maturation?
DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis.
What diseases are associated with defective ureter maturation?
Defective ureter maturation is associated with congenital anomalies of the kidney and urinary tract (CAKUT), including hydronephrosis and vesicoureteral reflux.
What is the role of Teashirt in ureter maturation?
Teashirt transcription factors regulate ureter myogenesis, which is essential for the development of the muscular wall of the ureter.
How is calcium signaling involved in ureter maturation?
Ca2+ signal dynamics in maturing ureteric bud- and collecting duct-derived organoid tubules play a role in functional maturation.
What model organisms are used to study ureter maturation?
Mouse models are widely used, including knockout mice for PTPRF and DLG1, as well as organoid cultures [2,6,7].
What is the connection between ureter maturation and CAKUT?
CAKUT often results from defects in ureter maturation, leading to structural and functional abnormalities of the urinary tract.
How can CRISPR be used to study ureter maturation?
CRISPR can create knockout, point mutation, knock-in, and overexpression models to dissect gene function in ureter maturation [1,2,7].
Conclusion
Ureter maturation (GO:0035799) is a critical developmental process that ensures the ureter becomes a fully functional tube for urine transport. Research has identified key molecular players, including LAR family phosphatases, DLG1, retinoic acid signaling, and Teashirt transcription factors, that orchestrate this process [2,4,7]. Defects in ureter maturation lead to congenital anomalies of the kidney and urinary tract, making it an important area of study for human health. Advances in CRISPR-based models and organoid systems continue to provide new insights into the mechanisms of ureter maturation and potential therapeutic targets.
References
- 1. Kispert A. 2025. Ureter development and associated congenital anomalies.. Nat Rev Nephrol 21(6):366-382 PMID: 40164775
- 2. Uetani N et al.. 2009. Maturation of ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases.. J Clin Invest 119(4):924-35 PMID: 19273906
- 4. Lye CM et al.. 2010. Ureter myogenesis: putting Teashirt into context.. J Am Soc Nephrol 21(1):24-30 PMID: 19926888
- 5. Amis ES Jr. 1991. Retroperitoneal fibrosis.. AJR Am J Roentgenol 157(2):321-9 PMID: 1853816
- 6. Carrisoza-Gaytán R et al.. 2025. Ca(2+) signal dynamics in maturing ureteric bud- and collecting duct-derived organoid tubules.. Am J Physiol Cell Physiol 329(6):C1842-C1856 PMID: 41026830
- 7. Kim ST et al.. 2014. DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis.. Dev Biol 390(2):160-9 PMID: 24699546
