Kidney Disease Research Updates
Secrets of Kidney Development Revealed in Zebrafish Research
With support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), researchers Rebecca Wingert, Ph.D., and Alan Davidson at the Center for Regenerative Medicine, Massachusetts General Hospital, have unraveled the sequence of steps in the development of the nephron, a microscopic structure in the kidneys where blood is filtered. Millions of nephrons in each kidney work collectively to remove waste and extra water from the blood in vertebrate animals. Studying zebrafish as a genetic model organism, Wingert and Davidson used genetic and chemical genetic models of retinoic acid (RA) deficiency to discover that RA modulates the formation of rostral progenitor formation.
In a paper published in Developmental Dynamics, Wingert and Davidson explain that kidney nephrons are composed of proximal and distal tubule segments that perform unique roles in excretion. The sequence of events that differ-entiates the segments as the nephron develops is not well understood. Wingert and Davidson used the zebrafish pronephros, an early version of the developing nephron, to study how the nephron divides into segments with different functions. “We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate,” wrote Wingert and Davidson in their article. At first, the nephron progenitors divide into two domains. The domains are then further divided into separate nephron segments.
At this point, the models of RA deficiency demonstrate how RA modulates rostral progeni-tor formation. To study the further development of the nephron, Wingert and Davidson knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Wingert and Davidson conclude, “Our results suggest a model whereby RA patterns the early field of nephron progenti-tors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs.”
The National Kidney and Urologic Diseases Information Clearinghouse, part of the NIDDK, offers fact sheets and easy-to-read booklets about the kidneys, kidney disease, and treatments for kidney failure. For more information or to obtain copies, visit www.kidney.niddk.nih.gov.
NIH Publication No. 12–4531
Page last updated June 26, 2012