Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
Rebecca A Wingert, Alan J Davidson


Kidney nephrons are composed of proximal and distal tubule segments that perform unique roles in excretion. The developmental pathways that establish nephron segment identities from renal progenitors are poorly understood. Here, we used the zebrafish pronephros to study nephron segmentation. We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate. Initially, two domains of nephron progenitors are established, then are subdivided and demarcate individual nephron segments. Using genetic and chemical genetic models of retinoic acid (RA) deficiency, we discovered that RA modulates rostral progenitor formation. To delineate downstream pathways, we knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs.


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Feb 22, 2008·Journal of the American Society of Nephrology : JASN·Andrew P McMahonUNKNOWN GUDMAP project
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Aug 22, 2008·Development·Pilar AlarcónJosé Luis Gómez-Skarmeta
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Feb 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Rosalind H MorleyFiona C Wardle

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Nov 20, 2012·Journal of the American Society of Nephrology : JASN·Richard W NaylorAlan J Davidson
Nov 6, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Richard W Naylor, Alan J Davidson
Oct 10, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Michael MarcotteMaxime Bouchard
Sep 6, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·M Cecilia CirioNeil A Hukriede
May 31, 2013·Development·Joseph J LancmanP Duc Si Dong
Mar 5, 2016·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Richard W Naylor, Alan J Davidson
Sep 10, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·Gary F Gerlach, Rebecca A Wingert
May 18, 2012·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Silke Pittlik, Gerrit Begemann
Jun 13, 2014·Genesis : the Journal of Genetics and Development·Paul T Kroeger, Rebecca A Wingert
Sep 14, 2014·Seminars in Nephrology·Elena LazzeriPaola Romagnani
Sep 14, 2014·Seminars in Nephrology·Veronika Sander, Alan J Davidson
Dec 3, 2014·Gene Expression Patterns : GEP·Robert McKeeRebecca A Wingert
Jun 20, 2015·Stem Cells International·Kristen K McCampbellRebecca A Wingert
May 15, 2015·Current Pathobiology Reports·Robert A McKee, Rebecca A Wingert
May 18, 2016·Journal of Morphology·Xiaodong ZhuZhihong Liu
Jul 9, 2016·Genesis : the Journal of Genetics and Development·Amanda N MarraRebecca A Wingert
Aug 31, 2016·Nature Reviews. Nephrology·Melissa H LittleMinoru Takasato
Sep 30, 2016·Scientific Reports·Mateus C AdolfiManfred Schartl
Sep 18, 2015·Cells·Audrey Desgrange, Silvia Cereghini
Mar 17, 2016·World Journal of Stem Cells·Bridgette E Drummond, Rebecca A Wingert
Nov 27, 2018·ELife·Joseph M ChambersRebecca A Wingert
Sep 25, 2018·The Journal of Pathology·Linda Holmquist MengelbierDavid Gisselsson
Mar 5, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Priya OuttandyDetlef Bockenhauer
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Dec 24, 2018·Scientific Reports·Elvin E MoralesRebecca A Wingert
Apr 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Amanda N MarraRebecca A Wingert
Nov 18, 2016·American Journal of Physiology. Renal Physiology·Simone Kersten, Francisco J Arjona
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