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Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

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Abstract

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.

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Acknowledgments

The authors wish to thank Elsevier, the American Society of Nephrology, and the American Physiological Society for permission to reprint some of the figures used in the publication. Some of the work presented was supported by grants from the National Institutes of Health, including R01 DK 070030, R01 DK 081128, and R01 DK095748 (C.M.B.).

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The authors declare that they have no conflicts of interest.

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Correspondence to Carlton M. Bates.

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Walker, K.A., Sims-Lucas, S. & Bates, C.M. Fibroblast growth factor receptor signaling in kidney and lower urinary tract development. Pediatr Nephrol 31, 885–895 (2016). https://doi.org/10.1007/s00467-015-3151-1

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