Dynamic regulation of Smad expression during mesenchyme to epithelium transition in the metanephric kidney

Mech Dev. 2002 Mar;112(1-2):207-11. doi: 10.1016/s0925-4773(01)00648-7.


Genetic studies have revealed a role for the transforming growth factor beta (TGFbeta) superfamily growth factors in development of the mouse kidney. In this study, we have characterized developmental expression of Smad proteins, the downstream effectors of TGFbeta superfamily ligands. Immunohistochemistry detecting Smads 1-5 and 8 was performed on 11.25-15.5 dpc kidney sections. We find that Smad proteins are readily detected in metanephric mesenchyme but are coordinately down-regulated in condensing mesenchyme and derivative structures such as renal vesicles. In order to define the stage at which down-regulation occurs, we used the heterologous inducer lithium chloride to promote condensation in isolated cultured mesenchymal explants and subsequently assayed expression of Smad 4. Down-regulation is complete in lithium chloride induced mesenchymal condensates, indicating that Smad regulation takes place at an early stage, prior to mesenchyme to epithelium transition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA-Binding Proteins / biosynthesis*
  • Epithelium / embryology*
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry
  • Kidney / embryology*
  • Mesoderm / metabolism*
  • Mice
  • Phosphoproteins / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad Proteins
  • Smad1 Protein
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad5 Protein
  • Smad8 Protein
  • Time Factors
  • Trans-Activators / biosynthesis*
  • Transforming Growth Factor beta / metabolism


  • DNA-Binding Proteins
  • Phosphoproteins
  • SMAD8 protein, human
  • Smad Proteins
  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Smad4 Protein
  • Smad4 protein, mouse
  • Smad4 protein, rat
  • Smad5 Protein
  • Smad5 protein, mouse
  • Smad8 Protein
  • Smad9 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta