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Alan Davidson, Ph.D. Assistant Professor of Medicine, Harvard Medical Schoolajdavidson@partners.org
Our long-term goals are to understand how the kidney forms during zebrafish embryonic development and how it regenerates following injury in the adult. These two processes appear to be linked, as the genes required for kidney formation in the embryo are re-expressed in adult kidneys in response to damage. From a large-scale functional genomics approach, we have collected over 100 genes expressed in the kidney including 29 transcription factors. Our analysis of the expression patterns of these genes has revealed that the zebrafish embryonic kidney is divided into molecularly distinct regions that are analogous to the segments of the mammalian nephron (glomerulus, proximal tubules, distal tubules, and collecting duct). We are using a combination of forward genetic screening, morpholino-mediated gene knock-down, and the generation of inducible transgenic lines to understand how these different functional segments are formed during embryogenesis.
To create a model of kidney damage in adult zebrafish we are using the nephrotoxin, gentamicin. Unlike mammals, zebrafish have remarkable regenerative capabilities and are able to completely re-grow kidney tissue following injury, including the induction of new nephrons. Understanding these differences in regenerative responses may lead to the discovery of new drugs or therapies to enhance renal repair in human patients with damaged or diseased kidneys. We are characterizing the molecular and pathophysiological changes that occur during zebrafish renal regeneration by expression analysis, histology, and the in vivo visualization of fluorescently-labeled kidney cells in transgenic fish.
Wingert, R.A. and Davidson, A.J. 2008. The zebrafish pronephros: a model to study nephron segmentation. Kidney international 73(10): 1120-1127.
Wingert, R.A., Selleck, R., Yu, J., Song, H.D., Chen, Z., Song, A., Zhou, Y., Thisse, B., Thisse, C., McMahon, A.P., and Davidson, A.J. 2007. The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros. PLoS genetics 3(10): 1922-1938.
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