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Publication
Renal blood flow and oxygenation drive nephron progenitor differentiation.
Authors Rymer C, Paredes J, Halt K, Schaefer C, Wiersch J, Zhang G, Potoka D, Vainio S,
Gittes GK, Bates CM, Sims-Lucas S
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal American journal of physiology. Renal physiology
Year 2014
Date Published 8/1/2014
Volume : Pages 307 : F337 - 45
PubMed Reference 24920757
Abstract During kidney development, the vasculature develops via both angiogenesis
(branching from major vessels) and vasculogenesis (de novo vessel formation).
The formation and perfusion of renal blood vessels are vastly understudied. In
the present study, we investigated the regulatory role of renal blood flow and
O2 concentration on nephron progenitor differentiation during ontogeny. To
elucidate the presence of blood flow, ultrasound-guided intracardiac
microinjection was performed, and FITC-tagged tomato lectin was perfused through
the embryo. Kidneys were costained for the vasculature, ureteric epithelium,
nephron progenitors, and nephron structures. We also analyzed nephron
differentiation in normoxia compared with hypoxia. At embryonic day 13.5
(E13.5), the major vascular branches were perfused; however, smaller-caliber
peripheral vessels remained unperfused. By E15.5, peripheral vessels started to
be perfused as well as glomeruli. While the interior kidney vessels were
perfused, the peripheral vessels (nephrogenic zone) remained unperfused.
Directly adjacent and internal to the nephrogenic zone, we found differentiated
nephron structures surrounded and infiltrated by perfused vessels. Furthermore,
we determined that at low O2 concentration, little nephron progenitor
differentiation was observed; at higher O2 concentrations, more differentiation
of the nephron progenitors was induced. The formation of the developing renal
vessels occurs before the onset of blood flow. Furthermore, renal blood flow and
oxygenation are critical for nephron progenitor differentiation.




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