title: Brg1 determines urothelial cell fate during ureter development.
abstract: Developing and adult ureters express the epigenetic regulator Brg1, but the role of Brg1 in ureter development is not well understood. We conditionally ablated Brg1 in the developing ureter using Hoxb7-Cre and found that Brg1 expression is upstream of p63, Pparγ, and sonic hedgehog (Shh) expression in the ureteral epithelium. In addition, epithelial stratification in the basal cells required Brg1-dependent p63 expression, whereas terminal differentiation of the umbrella cells required Brg1-dependent Pparγ expression. Furthermore, the loss of ureteric Brg1 resulted in failure of Shh expression, which correlated with reduced smooth muscle cell development and hydroureter. Taken together, we conclude that Brg1 expression unifies three aspects of ureter development: maintenance of the basal cell population, guidance for terminal differentiation of urothelial cells, and proper investment of ureteral smooth muscle cells.
authors: Department of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Robert M
authors: RM
authors: Weiss
authors: Songshan
authors: S
authors: Guo
authors: Alan
authors: A
authors: Shan
authors: Hongmei
authors: H
authors: Shi
authors: Rose-Anne
authors: RA
authors: Romano
authors: Satrajit
authors: S
authors: Sinha
authors: Lloyd G
authors: LG
authors: Cantley
authors: Jian-Kan
authors: JK
authors: Guo
mesh_terms: D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014513:Ureter / Q000254:growth & development* / Q000378:metabolism; D019459:Urothelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D047495:PPAR gamma; D010750:Phosphoproteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; C513194:Smarca4 protein, mouse; D004265:DNA Helicases