Metanephrogenic mesenchyme-to-epithelium transition induces profound expression changes of ion channels

Am J Physiol Renal Physiol. 2000 Jul;279(1):F65-76. doi: 10.1152/ajprenal.2000.279.1.F65.


The expression patterns of plasma membrane transporters that specify the epithelial cell type are acquired with ontogeny. To study this process during metanephrogenic mesenchyme-to-epithelium transition, branching ureteric buds with their adjacent mesenchymal blastema (mouse embryonic day E14) were dissected and explanted on a collagen matrix. In culture, induced mesenchymal cells condensed, aggregated, and converted to the comma- and S-shaped body. During in vitro condensation and aggregation, transcription factor Pax-2 protein was downregulated while the epithelial markers E-cadherin and beta-catenin proteins were upregulated. In addition, Wilms' tumor suppressor protein WT-1 was detectable upon condensation and downregulated in the S stage, where expression persisted in the long arm of the S. Patch-clamp, whole cell conductance (G, in nS/10 pF) of pre-epithelial condensed mesenchymal cells (n = 7) was compared with that of tubular proximal S-shaped-body epithelium (n = 6). Both stages expressed E-cadherin and WT-1 mRNA, as demonstrated by single-cell RT-PCR, testifying further to the epithelial as well as the nephrogenic commitment of the recorded cells. Mesenchymal cells exhibited whole cell currents (G = 6.7 +/- 1.3) with reversal potentials (V(rev), in mV) near equilibrium potential for Cl(-) (E(Cl)) (V(rev) = -40 +/- 7) suggestive of a high fractional Cl(-) conductance. Currents of the S-shaped-body cells (G = 4.0 +/- 1.1), in sharp contrast, had a V(rev) at E(K) (V(rev) = -82 +/- 6) indicating a high fractional K(+) conductance. Further, analysis of K(+)-selective whole cell tail currents and single-channel recording revealed a change in K(+) channel expression. Also, Kir6.1 K(+) channel mRNA and protein were downregulated between both stages, whereas K(v)LQT K(+) channel mRNA was abundant throughout. In conclusion, metanephrogenic mesenchyme-to-epithelium transition is accompanied by a profound reorganization of plasma membrane ion channel conductance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Aggregation
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Electric Conductivity
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Developmental*
  • Immunohistochemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Kidney / cytology
  • Kidney / embryology*
  • Kidney / metabolism*
  • Mesoderm / cytology*
  • Mesoderm / metabolism
  • Mice
  • PAX2 Transcription Factor
  • Potassium / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Potassium Channels, Voltage-Gated*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sodium Chloride / metabolism
  • Trans-Activators*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • WT1 Proteins
  • beta Catenin


  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Ion Channels
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Kcnq1 protein, mouse
  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • WT1 Proteins
  • beta Catenin
  • Sodium Chloride
  • Potassium