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

## TL;DR

Kindlins are essential for kidney development by regulating integrin and growth factor signaling during ureteric bud formation.

## Contribution

This study reveals that kindlins are crucial for both integrin function and growth factor signaling in ureteric bud development.

## Key findings

- Mice with β1 integrin mutations in the ureteric bud show mild kidney defects and moderate branching issues.
- Kindlin knockout in ureteric bud cells leads to complete absence of budding and failure to respond to growth factors.
- Kindlins are necessary for initial ureteric bud formation through integrin and growth factor regulation.

## Abstract

The kidney collecting system develops from the ureteric bud (UB), which undergoes multiple rounds of iterative branching. This process is controlled by growth factors and requires the interaction between the extracellular matrix and β1-containing integrin receptors. Integrin affinity for its ligands is regulated by integrin-binding proteins including kindlins, which bind well-defined motifs within the β subunit cytoplasmic tail. We show that mice expressing β1 integrins with mutations that abrogate kindlin binding in the developing UB have mild medullary hypoplasia and a moderate branching defect. Collecting duct (CD) cells expressing the same mutations in the β1 subunit have moderate tubulogenesis, spreading and adhesion defects, but show intact growth factor-dependent signaling. In contrast, mice lacking kindlins in the UB are anephric due to a complete absence of UB budding. Kindlin-knockout CD cells are unable to spread, adhere or respond to growth factors, irrespective of whether the integrins are bound to a ligand. Thus, in addition to regulating integrin function, kindlins mediate crucial growth factor signaling required for initial UB formation.

Summary: Kindlins mediate ureteric bud development by regulating both integrin- and growth factor-dependent functions.