Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes

Pediatr Res. 2002 May;51(5):551-8. doi: 10.1203/00006450-200205000-00002.


In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

Publication types

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

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Cell Differentiation
  • Cell Surface Extensions / physiology
  • Cell Surface Extensions / ultrastructure
  • Collagen / biosynthesis
  • Collagen / genetics
  • Endothelium, Vascular / physiology
  • Epithelial Cells / pathology
  • Extracellular Matrix Proteins / deficiency
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology
  • Gene Expression Regulation / genetics
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology
  • Humans
  • Kidney Glomerulus / cytology*
  • Kidney Glomerulus / physiology
  • LIM-Homeodomain Proteins
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Models, Biological
  • Nail-Patella Syndrome / genetics
  • Nail-Patella Syndrome / pathology*
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / pathology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transcription, Genetic*
  • Zebrafish


  • Extracellular Matrix Proteins
  • Homeodomain Proteins
  • LIM homeobox transcription factor 1 beta
  • LIM-Homeodomain Proteins
  • Protein Isoforms
  • Transcription Factors
  • Collagen