ArticleMechanisms of development
Stage specific requirement of Gfrα1 in the ureteric epithelium during kidney development.
Article in Mechanisms of development. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- Restoration of spermatogenesis is dependent on activation of a SPRY4-ERK checkpoint following germline stem cell damage†.Biology of reproduction · 2026Article
- Undifferentiated spermatogonia modulate their behavior via the expression of basement membrane protein laminin†.Biology of reproduction · 2026Article
- Restoration of Spermatogenesis is Dependent on Activation of a SPRY4-ERK Checkpoint Following Germline Stem Cell Damage.bioRxiv : the preprint server for biology · 2025Article
- Unlocking Genetic Mysteries during the Epic Sperm Journey toward Fertilization: Further ExpandingBiomolecules · 2024Review
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
- Defining Gene Function in Spermatogonial Stem Cells Through Conditional Knockout Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Postnatal prolongation of mammalian nephrogenesis by excess fetal GDNF.Development (Cambridge, England) · 2021Article
- Crosstalk between DNA methylation and histone acetylation triggers GDNF high transcription in glioblastoma cells.Clinical epigenetics · 2020Article
- Developmental pathology of congenital kidney and urinary tract anomalies.Clinical kidney journal · 2019Article
- Functional robustness of adult spermatogonial stem cells after induction of hyperactive Hras.PLoS genetics · 2019Article
- Centrosome amplification disrupts renal development and causes cystogenesis.The Journal of cell biology · 2018Article
- Regulation of Renal Differentiation by Trophic Factors.Frontiers in physiology · 2018Review
- Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary Tract.Journal of the American Society of Nephrology : JASN · 2018Review
- Cellular heterogeneity in the ureteric progenitor niche and distinct profiles of branching morphogenesis in organ development.Development (Cambridge, England) · 2017Article
- 7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome.Scientific reports · 2016Article
- Glial cell line-derived neurotrophic factor induces cell proliferation in the mouse urogenital sinus.Molecular endocrinology (Baltimore, Md.) · 2015Article
- To bud or not to bud: the RET perspective in CAKUT.Pediatric nephrology (Berlin, Germany) · 2014Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family receptor α1 (GFRα1) and forms a signaling complex with the receptor tyrosine kinase RET. GDNF-GFRα1-RET signaling activates cellular pathways that are required for normal induction of the ureteric bud (UB) from the Wolffian duct (WD). Failure of UB formation results in bilateral renal agenesis and perinatal lethality. Gfrα1 is expressed in both the epithelial and mesenchymal compartments of the developing kidney while Ret expression is specific to the epithelium. The biological importance of Gfrα1's wider tissue expression and its role in later kidney development are unclear. We discovered that conditional loss of Gfrα1 in the WD epithelium prior to UB branching is sufficient to cause renal agenesis. This finding indicates that Gfrα1 expressed in the nonepithelial structures cannot compensate for this loss. To determine Gfrα1's role in branching morphogenesis after UB induction we used an inducible Gfrα1-specific Cre-deletor strain and deleted Gfrα1 from the majority of UB tip cells post UB induction in vivo and in explant kidney cultures. We report that Gfrα1 excision from the epithelia compartment after UB induction caused a modest reduction in branching morphogenesis. The loss of Gfrα1 from UB-tip cells resulted in reduced cell proliferation and decreased activated ERK (pERK). Further, cells without Gfrα1 expression are able to populate the branching UB tips. These findings delineate previously unclear biological roles of Gfrα1 in the urinary tract and demonstrate its cell-type and stage-specific requirements in kidney development.
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