title: Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.
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.
authors: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Stephanie
authors: S
authors: Hum
authors: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Christopher
authors: C
authors: Rymer
authors: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Caitlin
authors: C
authors: Schaefer
authors: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Daniel
authors: D
authors: Bushnell
authors: Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Sunder
authors: S
authors: Sims-Lucas
mesh_terms: D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D007668:Kidney / Q000002:abnormalities / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009399:Nephrons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse