Brg1 determines urothelial cell fate during ureter development

J Am Soc Nephrol. 2013 Mar;24(4):618-26. doi: 10.1681/ASN.2012090902. Epub 2013 Feb 28.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Hedgehog Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • PPAR gamma / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ureter / growth & development*
  • Ureter / metabolism
  • Urothelium / cytology
  • Urothelium / metabolism*

Substances

  • Hedgehog Proteins
  • Nuclear Proteins
  • PPAR gamma
  • Phosphoproteins
  • Shh protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Trp63 protein, mouse
  • Smarca4 protein, mouse
  • DNA Helicases