Epithelial differentiation of metanephric mesenchymal cells after stimulation with hepatocyte growth factor or embryonic spinal cord

Sharon L. Karp, Alberto Ortiz-Arduan, Shaoran Li, Eric G. Neilson

Research output: Contribution to journalArticle

43 Scopus citations


Mammalian kidney emerges from metanephric mesenchyme following the insertion of a migrating ureteric bud. The pattern morphology of mesenchymal specialization during tubular segmentation is remarkably complex, and the relative contribution of pattern gradients from the microenvironment versus the instructive role of individual cells is not known. We have started to examine the differentiation of metanephric mesenchyme using cultures of metanephric ridge (MMR) cells from day 13.5 mouse embryos to investigate the conversion of mesenchyme toward kidney epithelium in vitro. One of our mesenchymal clones, MMR1, expresses little Pax2, uvomorulin, or cytokeratin but does express neural cell adhesion molecule, bcl2, and desmin; these are properties consistent with an early stem cell. Coculture of MMR1 cells with embryonic spinal cord leads to the induction of a more differentiated cell phenotype characterized by decreased expression of neural cell adhesion molecule, the appearance of uvomorulin, and the emergence of cytokeratin, all consistent with an evolution toward epithelium. We were also able to detect the hepatocyte growth factor receptor c-met on MMR1 cells by indirect immunofluorescence. When MMR1 cells were stimulated with hepatocyte growth factor, neural cell adhesion molecule expression decreased and uvomorulin appeared. This effect of hepatocyte growth factor, as a single cytokine, may be important in the early assemblage of kidney, since we were able to detect mRNA transcripts encoding c-met from mouse embryo metanephric kidneys.

Original languageEnglish (US)
Pages (from-to)5286-5290
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Jun 7 1994



  • cell culture
  • embryonic induction
  • kidney development
  • metanephros

ASJC Scopus subject areas

  • General

Cite this