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Kindlins regulate integrin- and growth factor-dependent ureteric bud formation.

Shensen Li1, Fabian Bock1,2,3, Olga Viquez1

  • 1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Development (Cambridge, England)
|January 26, 2026
PubMed
Summary
This summary is machine-generated.

Kindlins are crucial for kidney development, mediating essential growth factor signaling for ureteric bud formation and branching. Without kindlins, kidney development fails completely.

Keywords:
Branching morphogenesisGrowth factorIntegrinsKidney developmentKindlins

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Kidney collecting system development relies on ureteric bud (UB) branching.
  • This process involves extracellular matrix interactions with β1-integrin receptors.
  • Integrin binding affinity is modulated by kindlins, which interact with the β subunit tail.

Purpose of the Study:

  • To investigate the role of kindlins in regulating β1-integrin function during kidney development.
  • To elucidate the specific contributions of kindlin-mediated integrin binding to UB branching and collecting duct (CD) formation.

Main Methods:

  • Generation of mice with mutated β1-integrins lacking kindlin binding sites in the UB.
  • Analysis of kidney development and CD cell function in these mice.
  • Generation and analysis of kindlin-knockout mice and CD cells.

Main Results:

  • Mice with kindlin-binding deficient β1-integrins showed medullary hypoplasia and moderate branching defects.
  • Mutant CD cells exhibited impaired tubulogenesis, spreading, and adhesion but retained growth factor signaling.
  • Kindlin-knockout mice were anephric, indicating a complete failure of UB budding.
  • Kindlin-knockout CD cells failed to spread, adhere, or respond to growth factors, even with ligand-bound integrins.

Conclusions:

  • Kindlins regulate both integrin function and critical growth factor signaling pathways.
  • Kindlins are essential for initial ureteric bud formation and subsequent kidney development.
  • Distinct roles for kindlin-binding integrins versus kindlin proteins themselves in kidney development.