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Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning

Hum, S and Rymer, C and Schaefer, C and Bushnell, D and Sims-Lucas, S (2014) Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning. PLoS ONE, 9 (2).

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Abstract

The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. © 2014 Hum et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hum, Sswh23@pitt.eduSWH23
Rymer, C
Schaefer, Ccms198@pitt.eduCMS198
Bushnell, Ddab152@pitt.eduDAB152
Sims-Lucas, S
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSingh, Shree RamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 5 February 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0088400
Schools and Programs: School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 23 Jun 2014 21:12
Last Modified: 07 Jul 2020 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/21902

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