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Mechanobiology and signaling

Multiple aspects of zebrafish kidney development involve mechanobiology and physical stimuli to promote morphogenesis.

The kidney glomerular capillary tuft provides the input for blood filtration by the kidney. We discovered an essential role for vascular fluid shear force in capillary tuft formation in the kidney using a panel of zebrafish mutants lacking blood flow, taking unique advantage of the fact that zebrafish can survive to hatching without cardiac function.

Kidney function is defined by the properties of distinct nephron segments. Using live, in vivo cell imaging, we discovered that nephron morphogenesis is driven by collective epithelial cell migration that generates proximal tubule convolutions and defines the final position of nephron segment boundaries [46]. We showed that cell migration was signaled by the onset of nephron filtration and luminal fluid flow, linking nephron morphogenesis with nephron function.

Further, we showed that tubule cell proliferation was closely integrated with cell migration owing to migration-induced cell stretch, demonstrating that morphogenesis can be a self-regulating process. In our most recent work we show that collective cell migration is one of the earliest responses to tubule injury, preceding cell proliferation. This work has important implications for early interventions after acute kidney injury, a major factor in progression to chronic kidney disease and kidney failure.