GO:0072208 metanephric smooth muscle tissue development: Developmental Process, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0072208 describes the progression of smooth muscle tissue within the metanephros (the definitive kidney) from its formation to mature structure.
• This process is essential for establishing the renal vasculature and ureteric peristalsis, and defects are linked to congenital anomalies of the kidney and urinary tract (CAKUT).
• Key signaling pathways include BMP4, angiopoietins, and Wnt/β-catenin, which regulate smooth muscle differentiation and investment [1,4,7].
• Periostin and stromal transcription factor 21 (Osr1) are critical regulators of smooth muscle development in the metanephros [6,7].
• Renin lineage cells contribute to the smooth muscle coat of renal arterioles during nephrogenesis.
• Disruption of smooth muscle development leads to ureteropelvic junction obstruction and hydronephrosis in animal models.
Description
The metanephros is the definitive mammalian kidney, and its development requires coordinated interactions between the ureteric bud and the metanephric mesenchyme. A critical but often overlooked component of this process is the formation of smooth muscle tissue, which invests the ureter, renal pelvis, and intrarenal vasculature. GO:0072208, metanephric smooth muscle tissue development, captures the biological processes that drive the specification, differentiation, and maturation of smooth muscle cells within the metanephros. Understanding this term is essential for researchers studying kidney organogenesis, congenital anomalies, and vascular development. Smooth muscle tissue in the metanephros is not merely a structural support; it provides peristaltic force for urine transport and regulates renal blood flow. Defects in its development are associated with ureteropelvic junction obstruction, hydronephrosis, and other CAKUT phenotypes. Moreover, smooth muscle cells share a common mesenchymal progenitor pool with other renal stromal lineages, making their study relevant to stromal-epithelial signaling. Recent studies have identified key molecular players, including BMP4, angiopoietins, periostin, and transcription factors such as Osr1, that orchestrate this process [1,4,6,7]. This article synthesizes the current understanding of GO:0072208, highlighting its mechanisms, key genes, disease relevance, and experimental approaches for investigation.
metanephric smooth muscle tissue development At A Glance
| GO ID | GO:0072208 |
|---|---|
| GO term | metanephric smooth muscle tissue development |
| Ontology | biological_process |
| Synonym | None |
| Major function | Formation and maturation of smooth muscle tissue in the metanephros, essential for ureteric peristalsis and renal vascular tone |
| Related processes | Mesenchymal-epithelial interactions, smooth muscle cell differentiation, angiogenesis |
| Key signaling pathways | BMP4, Angiopoietin-Tie2, Wnt/β-catenin, Notch |
| Associated cell types | Smooth muscle cells, pericytes, renin lineage cells, stromal progenitors |
| Disease relevance | CAKUT, ureteropelvic junction obstruction, hydronephrosis, renal vascular abnormalities |
What Is GO:0072208?
GO:0072208, metanephric smooth muscle tissue development, is defined as the process whose specific outcome is the progression of smooth muscle in the metanephros over time, from its formation to the mature structure. In simpler terms, it encompasses all the cellular and molecular events that lead to the creation of functional smooth muscle tissue within the developing kidney, including cell specification, proliferation, migration, differentiation, and maturation.
Why Is metanephric smooth muscle tissue development Important in Cell Biology?
Metanephric smooth muscle tissue development is crucial for normal kidney function because smooth muscle cells provide the contractile force for urine transport and regulate blood flow in renal arterioles. Disruption of this process leads to congenital anomalies such as ureteropelvic junction obstruction, which can cause hydronephrosis and renal failure. Additionally, smooth muscle cells are part of the renal stroma and participate in reciprocal signaling with epithelial cells, influencing nephron formation and patterning. Understanding GO:0072208 therefore has direct implications for developmental biology, nephrology, and urology.
• Smooth muscle tissue in the metanephros is required for peristaltic movement of urine from the renal pelvis to the ureter.
• Defective smooth muscle development is a major cause of ureteropelvic junction obstruction and hydronephrosis.
• Smooth muscle cells contribute to the renal vascular tree, affecting blood pressure and filtration.
• The process is regulated by conserved signaling pathways such as BMP4 and angiopoietins, offering therapeutic targets [1,4].
• Renin lineage cells can differentiate into smooth muscle cells, linking renal endocrine function to vascular development.
• Stromal transcription factors like Osr1 coordinate smooth muscle differentiation with overall kidney patterning.
• Periostin, an extracellular matrix protein, modulates smooth muscle investment of the ureter.
• Abnormal smooth muscle development is associated with CAKUT, a leading cause of pediatric kidney failure.
• Studying this process aids in tissue engineering of kidney and ureter replacements.
• Animal models with disrupted smooth muscle development provide insights into human congenital anomalies [4,5].
What Happens During metanephric smooth muscle tissue development?
Specification of Smooth Muscle Progenitors
In simple terms: Early in kidney development, certain mesenchymal cells are told to become smooth muscle cells.
Smooth muscle progenitors in the metanephros arise from the metanephric mesenchyme and surrounding stroma. Signaling from the ureteric bud and adjacent epithelia, including Wnt/β-catenin and BMP4, induces the expression of smooth muscle markers such as alpha-smooth muscle actin (ACTA2) and transgelin (TAGLN) [4,7]. The transcription factor Osr1 (odd-skipped related 1) is essential for maintaining the stromal progenitor pool and directing cells toward smooth muscle fate. Disruption of BMP4 signaling in mice results in reduced smooth muscle investment of the ureter, demonstrating its requirement for progenitor specification.
Migration and Investment of the Ureter and Vasculature
In simple terms: The newly specified smooth muscle cells move to wrap around the ureter and developing blood vessels.
After specification, smooth muscle progenitors migrate and invest the ureteric epithelium and renal arteries [4,6]. This investment is guided by extracellular matrix components such as periostin, which is expressed in the ureteric mesenchyme and promotes smooth muscle differentiation and alignment. Angiopoietins, particularly Angiopoietin-1 and -2, regulate the interaction between endothelial cells and smooth muscle cells during vascular development in the kidney. In the absence of proper investment, ureteric peristalsis is impaired, leading to urine stasis.
Differentiation and Maturation of Smooth Muscle Cells
In simple terms: The cells mature into fully functional smooth muscle that can contract.
Differentiation of smooth muscle cells involves the upregulation of contractile proteins such as smooth muscle myosin heavy chain (MYH11), calponin (CNN1), and smoothelin (SMTN) [4,8]. This process is regulated by transcription factors including serum response factor (SRF) and myocardin (MYOCD). Renin lineage cells have been shown to differentiate into smooth muscle cells during nephrogenesis, contributing to the mural cell coat of renal arterioles. Maturation is accompanied by the formation of dense bodies and gap junctions, enabling coordinated contraction.
Integration with Renal Vascular and Stromal Networks
In simple terms: Smooth muscle cells become part of the kidney's support structure and blood vessel network.
Smooth muscle cells integrate with pericytes and other stromal cells to form the renal vascular tree [1,7]. Angiopoietin-Tie2 signaling is critical for stabilizing these interactions and maintaining vascular integrity. Stromal transcription factor 21 (Osr1) regulates the development of the renal stroma, which in turn influences smooth muscle investment. Defects in this integration can lead to vascular abnormalities and impaired kidney function.
Functional Maturation and Peristaltic Activity
In simple terms: The smooth muscle becomes fully functional, able to push urine along.
Mature smooth muscle tissue in the metanephros exhibits spontaneous electrical activity and responds to neurotransmitters and hormones to generate peristaltic waves. This function is essential for transporting urine from the renal pelvis to the bladder. In animal models where smooth muscle development is disrupted, such as BMP4 antagonist-treated mice, ureteropelvic junction obstruction and hydronephrosis develop, highlighting the functional importance of this process.
Key Genes Involved in GO:0072208 metanephric smooth muscle tissue development
The following genes and proteins have been experimentally implicated in metanephric smooth muscle tissue development, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BMP4 | Induces smooth muscle differentiation and investment of the ureter | BMP4 antagonism disrupts smooth muscle development, leading to ureteropelvic junction obstruction |
| ACTA2 | Smooth muscle actin, a marker of differentiated smooth muscle cells | Used to assess smooth muscle differentiation in vivo and in vitro |
| TAGLN | Transgelin, a smooth muscle-specific protein | Marker for smooth muscle cell maturation |
| MYH11 | Smooth muscle myosin heavy chain, contractile protein | Indicator of mature smooth muscle function |
| CNN1 | Calponin, regulates smooth muscle contraction | Marker of differentiated smooth muscle |
| SMTN | Smoothelin, a cytoskeletal protein in mature smooth muscle | Distinguishes mature from synthetic smooth muscle |
| MYOCD | Myocardin, coactivator of SRF for smooth muscle gene expression | Master regulator of smooth muscle differentiation |
| SRF | Serum response factor, transcription factor | Drives expression of smooth muscle contractile genes |
| POSTN | Periostin, extracellular matrix protein | Promotes smooth muscle differentiation and investment of the ureter |
| ANGPT1 | Angiopoietin-1, vascular stabilizing factor | Regulates smooth muscle-endothelial interactions in kidney |
| ANGPT2 | Angiopoietin-2, vascular destabilizing factor | Modulates smooth muscle investment during development |
| OSR1 | Odd-skipped related 1, stromal transcription factor | Regulates renal stroma development including smooth muscle progenitors |
| REN | Renin, marker of renin lineage cells | Renin lineage cells differentiate into smooth muscle cells |
| PDGFRB | Platelet-derived growth factor receptor beta | Regulates pericyte and smooth muscle recruitment |
| NOTCH3 | Notch receptor 3 | Regulates arterial smooth muscle differentiation |
| TIE2 (TEK) | Endothelial receptor for angiopoietins | Mediates angiopoietin signaling in vascular smooth muscle |
| WNT4 | Wnt family member 4 | Regulates mesenchymal-to-epithelial transition and stromal signaling |
| CTNNB1 | Beta-catenin, Wnt signaling effector | Integrates Wnt/β-catenin signaling in stromal development |
How Is metanephric smooth muscle tissue development Regulated?
Metanephric smooth muscle tissue development is regulated by a complex interplay of signaling pathways and transcription factors. BMP4 signaling is essential for smooth muscle investment of the ureter; its antagonism leads to reduced smooth muscle and ureteropelvic junction obstruction. Angiopoietin-Tie2 signaling regulates the interaction between endothelial cells and smooth muscle cells, influencing vascular stability. Wnt/β-catenin signaling, acting through stromal transcription factors such as Osr1, controls the expansion and differentiation of smooth muscle progenitors. Periostin, an extracellular matrix protein, promotes smooth muscle differentiation and alignment in the ureter. Additionally, renin lineage cells can differentiate into smooth muscle cells under the control of yet-to-be-defined cues. These pathways are tightly coordinated to ensure proper timing and spatial organization of smooth muscle tissue.
metanephric smooth muscle tissue development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BMP4 | Ureteropelvic junction obstruction, hydronephrosis | BMP4 conditional knockout mouse or BMP antagonist treatment |
| ANGPT1/ANGPT2 | Renal vascular abnormalities, impaired angiogenesis | Angiopoietin knockout or overexpression mouse models |
| OSR1 | CAKUT, stromal defects | Osr1 conditional knockout mouse |
| POSTN | Ureteric smooth muscle defects | Periostin knockout mouse |
| REN | Renal vascular development, hypertension | Renin lineage tracing and ablation models |
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Disruption of metanephric smooth muscle tissue development is a known cause of CAKUT, particularly ureteropelvic junction obstruction (UPJO). In mouse models, antagonism of BMP4 signaling results in reduced smooth muscle investment of the ureter and subsequent hydronephrosis, mimicking human UPJO. These findings suggest that genes regulating smooth muscle development are candidate susceptibility factors for CAKUT.
Renal Vascular Abnormalities
Smooth muscle cells are critical for the structural integrity and contractility of renal arterioles. Defects in angiopoietin signaling, which regulates smooth muscle-endothelial interactions, can lead to vascular abnormalities and impaired kidney function. Understanding these mechanisms may provide insights into hypertension and renal vascular diseases.
Hydronephrosis and Obstructive Uropathy
Impaired smooth muscle development leads to ineffective peristalsis and urine stasis, resulting in hydronephrosis. This condition can cause progressive kidney damage and is a common reason for pediatric nephrology referral. Research into the molecular basis of smooth muscle development may identify therapeutic targets to prevent or treat obstructive uropathy.
From metanephric smooth muscle tissue development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate smooth muscle differentiation? | Conditional knockout of gene X in metanephric mesenchyme (e.g., using Six2-Cre) |
| What is the effect of a point mutation in gene Y on smooth muscle function? | Knock-in mouse carrying the point mutation |
| Can overexpression of gene Z rescue smooth muscle defects? | Transgenic overexpression of gene Z in smooth muscle lineage |
| Where and when is protein W expressed during smooth muscle development? | Tagged knock-in reporter (e.g., GFP) for gene W |
| What are the downstream targets of transcription factor V? | ChIP-seq and RNA-seq in sorted smooth muscle cells from knockout and wild-type |
| Does gene U contribute to ureteric peristalsis? | Ex vivo ureter peristalsis assay in knockout mice |
How to Study the metanephric smooth muscle tissue development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Immunofluorescence | Protein expression and localization | Detect smooth muscle markers in tissue sections |
| In situ hybridization | mRNA expression patterns | Localize transcripts of regulatory genes |
| Lineage tracing | Cell fate and contribution | Track progenitor cells during development |
| Single-cell RNA-seq | Transcriptomic heterogeneity | Identify smooth muscle subtypes and regulators |
| Ex vivo peristalsis assay | Contractile function | Assess ureteric smooth muscle function |
| ChIP-seq | Transcription factor binding sites | Map SRF or myocardin binding in smooth muscle cells |
| Western blot | Protein expression levels | Quantify smooth muscle contractile proteins |
Lineage Tracing and Genetic Fate Mapping
Lineage tracing using Cre-lox systems (e.g., Ren-Cre, Osr1-Cre) allows researchers to follow the fate of smooth muscle progenitors during metanephric development [7,8]. This method has revealed that renin lineage cells contribute to the smooth muscle coat of renal arterioles.
Immunohistochemistry and In Situ Hybridization
These techniques are used to visualize the spatiotemporal expression of smooth muscle markers (e.g., ACTA2, MYH11) and regulatory genes (e.g., BMP4, POSTN) in kidney sections [4,6]. They provide spatial context for smooth muscle development.
Transcriptomics and Single-Cell RNA Sequencing
RNA sequencing of sorted smooth muscle cells or single-cell RNA-seq of developing kidneys can identify novel regulators and heterogeneity within smooth muscle populations. This approach has been used to define stromal cell subtypes and their differentiation trajectories.
Functional Assays for Smooth Muscle Contractility
Ex vivo ureter peristalsis assays and wire myography measure the contractile function of smooth muscle tissue. These assays can detect functional deficits in mutant models, linking molecular changes to physiological outcomes.
How CRISPR Can Be Used to Study GO:0072208 metanephric smooth muscle tissue development
Knockout
CRISPR-Cas9 knockout of candidate genes (e.g., Bmp4, Osr1, Postn) in mouse models or cell lines can reveal their requirement for metanephric smooth muscle development [4,6,7]. Conditional knockout using Cre drivers specific to the metanephric mesenchyme or smooth muscle lineage allows spatial and temporal control.
Point Mutation
Introducing precise point mutations (e.g., in Bmp4 or Osr1) via CRISPR base editing or homology-directed repair can model human variants associated with CAKUT and test their impact on smooth muscle differentiation [4,7]. This approach helps distinguish pathogenic from benign polymorphisms.
Knock-in
Knock-in of reporter genes (e.g., GFP, lacZ) or epitope tags into endogenous loci (e.g., Acta2, Myh11) enables visualization and purification of smooth muscle cells during development. Knock-in of human disease alleles into mouse orthologs can create humanized models for studying smooth muscle pathology.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression of pro-smooth muscle genes (e.g., Myocd, Postn) can drive ectopic smooth muscle differentiation or rescue loss-of-function phenotypes [4,6]. This is useful for testing sufficiency of a gene in promoting smooth muscle development.
How EDITGENE Supports metanephric smooth muscle tissue development Research
Researchers studying metanephric smooth muscle tissue development-related genes often need to determine whether a candidate gene is causally involved in smooth muscle specification, differentiation, or function. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research, from gene knockout to precise point mutations and overexpression models.
Contact EDITGENE today to design your custom CRISPR model for metanephric smooth muscle tissue development research.
Frequently Asked Questions About metanephric smooth muscle tissue development
What is GO:0072208?
GO:0072208 is the Gene Ontology term for metanephric smooth muscle tissue development, defined as the process whose specific outcome is the progression of smooth muscle in the metanephros over time, from its formation to the mature structure.
What genes are involved in metanephric smooth muscle tissue development?
Key genes include BMP4, ACTA2, TAGLN, MYH11, CNN1, SMTN, MYOCD, SRF, POSTN, ANGPT1, ANGPT2, OSR1, REN, PDGFRB, NOTCH3, TEK, WNT4, and CTNNB1, as identified in developmental studies [1,4,6,7,8].
Why is smooth muscle important in kidney development?
Smooth muscle tissue provides peristaltic force for urine transport and regulates renal blood flow; its defects cause ureteropelvic junction obstruction and hydronephrosis.
What signaling pathways regulate metanephric smooth muscle development?
BMP4, angiopoietin-Tie2, Wnt/β-catenin, and Notch pathways are major regulators, along with transcription factors like Osr1 and myocardin [1,4,7].
How can I study metanephric smooth muscle tissue development?
Common methods include lineage tracing, immunohistochemistry, single-cell RNA-seq, ex vivo peristalsis assays, and CRISPR-based gene editing in mouse models or cell lines [4,6,7,8].
What diseases are associated with defective metanephric smooth muscle development?
Congenital anomalies of the kidney and urinary tract (CAKUT), ureteropelvic junction obstruction, hydronephrosis, and renal vascular abnormalities [1,4].
What is the role of BMP4 in metanephric smooth muscle development?
BMP4 signaling is required for smooth muscle investment of the ureter; its antagonism leads to reduced smooth muscle and ureteropelvic junction obstruction in mice.
How do renin lineage cells contribute to smooth muscle development?
Renin lineage cells can differentiate into smooth muscle cells during nephrogenesis, contributing to the mural cell coat of renal arterioles.
What is the function of periostin in kidney smooth muscle development?
Periostin, an extracellular matrix protein, promotes smooth muscle differentiation and alignment in the ureter.
Can CRISPR be used to model metanephric smooth muscle development?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models in mice or cell lines can be used to study gene function in smooth muscle development [4,6,7].
Conclusion
GO:0072208, metanephric smooth muscle tissue development, is a vital developmental process that ensures proper formation of smooth muscle in the kidney and urinary tract. It is regulated by a network of signaling pathways and transcription factors, with BMP4, angiopoietins, Wnt/β-catenin, and Osr1 playing central roles [1,4,7]. Defects in this process lead to congenital anomalies such as ureteropelvic junction obstruction and hydronephrosis. Continued research using advanced CRISPR models and multi-omics approaches will further elucidate the molecular mechanisms and identify therapeutic targets for related diseases.
References
- 1. Woolf AS et al.. 2009. Roles of angiopoietins in kidney development and disease.. J Am Soc Nephrol 20(2):239-44 PMID: 18799719
- 3. Woolf AS et al.. 2002. Cell turnover in normal and abnormal kidney development.. Nephrol Dial Transplant 17 Suppl 9:2-4 PMID: 12386272
- 4. Wang GJ et al.. 2009. Antagonism of BMP4 signaling disrupts smooth muscle investment of the ureter and ureteropelvic junction.. J Urol 181(1):401-7 PMID: 19010499
- 6. Sorocos K et al.. 2011. Expression patterns and roles of periostin during kidney and ureter development.. J Urol 186(4):1537-44 PMID: 21855915
- 7. Finer G et al.. 2022. Stromal Transcription Factor 21 Regulates Development of the Renal Stroma via Interaction with Wnt/β-Catenin Signaling.. Kidney360 3(7):1228-1241 PMID: 35919523
- 8. Kessel F et al.. 2021. Patterns of differentiation of renin lineage cells during nephrogenesis.. Am J Physiol Renal Physiol 321(3):F378-F388 PMID: 34338032
