Semaphorins in kidney development and disease: Modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk

Kimberly Reidy, Alda Tufro

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Semaphorins are guidance proteins that play important roles in organogenesis and disease. Expression of class 3 semaphorins and their receptors is regulated during kidney development. Gain- and loss-of-function experiments demonstrated that tight semaphorin3a gene dosage is required for podocyte differentiation, and for the establishment of a normal glomerular filtration barrier. Sema3a modulates kidney vascular patterning acting as a negative regulator of endothelial cell migration and survival. Excess podocyte semaphorin3a expression causes glomerular disease in mice. In addition, Sema3a is a negative regulator of ureteric bud branching, whereas Sema3c is a positive regulator of ureteric bud and endothelial cell branching morphogenesis. In summary, secreted semaphorins modulate ureteric bud branching, vascular patterning, and podocyte-endothelial crosstalk, suggesting that they play a role in renal disease. Understanding the signaling pathways downstream from semaphorin receptors will provide insight into the mechanism of action of semaphorins in renal pathology.

Original languageEnglish (US)
Pages (from-to)1407-1412
Number of pages6
JournalPediatric Nephrology
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2011

Keywords

  • Branching morphogenesis
  • Semaphorin3a
  • Semaphorin3c
  • Vascular patterning

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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