title: The transcription factor Sry-related HMG box-4 (SOX4) is required for normal renal development in vivo.
abstract: BACKGROUND
  The DNA-binding transcription factor Wilms' Tumor Suppressor-1 (WT1) plays an essential role in nephron progenitor differentiation during renal development. We previously used Wt1 chromatin-immunoprecipitation coupled to microarray (ChIP-chip) to identify novel Wt1 target genes that may regulate nephrogenesis in vivo. We discovered that all three members of the SoxC subfamily, namely, Sox4, Sox11, and Sox12, are bound by Wt1 in mouse embryonic kidneys in vivo. SoxC genes play master roles in determining neuronal and mesenchymal progenitor cell fate in a multitude of developmental processes, but their function in the developing kidney is largely unknown.
  
  
  RESULTS
  Here we show that all three SoxC genes are expressed in the nephrogenic lineages during renal development. Conditional ablation of Sox4 in nephron progenitors and their cellular descendants (Sox4(nephron-) mice) results in a significant reduction in nephron endowment. By postnatal day (P)7, Sox4(nephron-) renal corpuscles exhibit reduced numbers of Wt1+ podocytes together with loss of expression of the slit diaphragm protein nephrin. Sox4(nephron-) mice develop early-onset proteinacious glomerular injury within 2 weeks of birth progressing to end-stage renal failure within 5-9 months.
  
  
  CONCLUSIONS
  Collectively, our results demonstrate an essential requirement of Sox4 for normal renal development in vivo.
authors.affiliation: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
authors.forename: Jez
authors.initials: J
authors.lastname: Huang
authors.forename: Michel
authors.initials: M
authors.lastname: Arsenault
authors.forename: Martin
authors.initials: M
authors.lastname: Kann
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Mendez
authors.forename: Monique
authors.initials: M
authors.lastname: Saleh
authors.forename: Dorota
authors.initials: D
authors.lastname: Wadowska
authors.forename: Mary
authors.initials: M
authors.lastname: Taglienti
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ho
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: David
authors.initials: D
authors.lastname: Sims
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spears
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lopez
authors.forename: Glenda
authors.initials: G
authors.lastname: Wright
authors.forename: Sunny
authors.initials: S
authors.lastname: Hartwig
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology*; D007678:Kidney Glomerulus / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009399:Nephrons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051437:Renal Insufficiency / Q000235:genetics; D055751:SOXC Transcription Factors / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C529443:Sox12 protein, mouse; C489990:Sox4 protein, mouse; D025721:WT1 Proteins