Abstract: SA-PO0002
SRGAP1 Regulates Kidney Morphogenesis Downstream of SLIT2-ROBO2 Signaling
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Yan, Kun, Boston University, Boston, Massachusetts, United States
- Xu, Chutian, Boston University, Boston, Massachusetts, United States
- Dodd, Laura, Boston University, Boston, Massachusetts, United States
- Vurkac, Omer Ege, Boston University, Boston, Massachusetts, United States
- Cai, Cynthia, Boston University, Boston, Massachusetts, United States
- Chandiri, Sarayu, Boston University, Boston, Massachusetts, United States
- Mantri, Ria, Boston University, Boston, Massachusetts, United States
- Park, Mingi, Boston University, Boston, Massachusetts, United States
- Fang, Eric Yuting, Boston University, Boston, Massachusetts, United States
- Lu, Eddy, Boston University, Boston, Massachusetts, United States
- Young, Kyle, Boston University, Boston, Massachusetts, United States
- Zhang, Simon, Boston University, Boston, Massachusetts, United States
- Fan, Xueping, Boston University, Boston, Massachusetts, United States
- Salant, David J., Boston University, Boston, Massachusetts, United States
- Kumar, Sudhir, Boston University, Boston, Massachusetts, United States
- Lu, Weining, Boston University, Boston, Massachusetts, United States
Background
Mutations in SLIT2 or ROBO2 cause congenital anomalies of the kidney and urinary tract (CAKUT), and SRGAP1 is a signaling component downstream of the SLIT-ROBO pathway to inhibit actin polymerization. Rare SRGAP1 variants have been reported in patients with CAKUT, but the role of SRGAP1 during kidney development remains unclear. We tested the hypothesis that SRGAP1 is necessary for kidney morphogenesis downstream of SLIT2-ROBO2.
Methods
We analyzed kidney development and adult kidney structure in Srgap1 knockout (KO) and wild-type (WT) mice. Gross anatomy was evaluated at birth and in adults (8-12 weeks). Histology (H&E, PAS) and immunofluorescence (AQP2, SIX2, WT1) were performed on neonatal and adult kidneys to assess corticomedullary organization, papilla formation, collecting duct morphology, and nephron progenitor organization. Urine was analyzed by SDS-PAGE for albuminuria, and blood chemistries were measured to assess renal function. Quantitative assessments were compared between genotypes using appropriate statistical tests.
Results
Srgap1 KOs were born at Mendelian ratios. Approximately 30% of Srgap1 KO mice exhibited unilateral hydronephrosis by gross inspection. Adult Srgap1 KO kidneys (8-12 weeks) showed disrupted corticomedullary architecture and abnormal papillae compared with WT controls. AQP2 immunofluorescence revealed defective collecting duct/papilla morphogenesis, including reduced AQP2-positive collecting duct extension into the papilla. Neonatal SIX2 staining demonstrated impaired cap mesenchyme organization in Srgap1 KOs, with altered SIX2+ niche patterning and reduced nephron progenitor clustering. Urine SDS-PAGE identified mild albuminuria in Srgap1 KO mice, suggesting compromised glomerular filtration barrier.
Conclusion
Loss of SRGAP1 disrupts renal morphogenesis in mice, leading to corticomedullary disorganization, defective papilla and collecting duct development, impaired organization of cap mesenchyme, and mild albuminuria. These data place SRGAP1 downstream of SLIT2–ROBO2 signaling during kidney development and provide in vivo genetic evidence linking SRGAP1 perturbation to CAKUT-relevant phenotypes.
Funding
- NIDDK Support