α-Parvin regulation of cell rearrangement is critical for ureteric bud branching morphogenesis
All branched tubular structures, including the kidney collecting system, are formed by branching morphogenesis, a process that includes tip branching and trunk narrowing. Tight control of cell movement and rearrangement is a prerequisite for branching morphogenesis. The role of integrin-associated adhesion proteins in coordinating actin dynamics and cell rearrangement during branching morphogenesis is poorly understood. Here, we used three-dimensional live imaging of mouse ureteric bud branching to show that α-parvin, a component of the integrin binding ILK-PINCH-parvin complex, regulates tip branching and tubule thinning by inhibiting excessive cell adhesion and actin polymerization. Mechanistically, α-parvin promotes actin turnover by inhibiting activation of the small guanosine triphosphatases RhoA and Cdc42, which in turn enhances the severing function of the actin regulatory protein, cofilin. These results underscore the importance of adhesion protein-regulated actin dynamics in the critical process of cell rearrangement, which is required for branching morphogenesis.
Authors
- Gema Bolás (ORCID: https://orcid.org/0000-0001-7809-1959)
- Kyle L. Brown (ORCID: https://orcid.org/0000-0002-7671-1912)
- Roy Zent (ORCID: https://orcid.org/0000-0003-2983-8133)
- Sara A. Wickström (ORCID: https://orcid.org/0000-0001-6383-6292)
- Fabian Bock (ORCID: https://orcid.org/0000-0002-0788-2945)
- Wanying Zhu
- Meiling Melzer (ORCID: https://orcid.org/0009-0001-3935-3159)
- Glenda Mernaugh (ORCID: https://orcid.org/0000-0003-0463-9509)
- Eloi Montañez (ORCID: https://orcid.org/0000-0003-4059-5056)
- Xinyu Dong (ORCID: https://orcid.org/0000-0002-3017-2634)
- Shensen Li (ORCID: https://orcid.org/0000-0003-1592-3011)
- Ambra Pozzi (ORCID: https://orcid.org/0000-0001-8502-1481)
- Ali Hashmi
- Nada Bulus (ORCID: https://orcid.org/0009-0007-8783-7856)
- Colton Miller
- Olga Viquéz
Institutions
- University of Helsinki (FI)
- Vanderbilt University (US)
- Bellvitge University Hospital (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Department of Veterans Affairs (AU)
- Max Planck Institute for Molecular Biomedicine (DE)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-09-18
- DOI
- https://doi.org/10.1126/sciadv.aec9007
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Veterans Affairs
- American Society of Nephrology
- Biocenter Finland
- National Institutes of Health