Semaphorins in kidney development and disease

Modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk

Kimberly J. Reidy, Alda Tufro

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 2011

Fingerprint

Semaphorins
Podocytes
Kidney Diseases
Morphogenesis
Blood Vessels
Semaphorin-3A
Kidney
Glomerular Filtration Barrier
Endothelial Cells
Gene Dosage
Organogenesis
Cell Movement
Cell Survival
Pathology
Proteins

Keywords

  • Branching morphogenesis
  • Semaphorin3a
  • Semaphorin3c
  • Vascular patterning

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "Semaphorins in kidney development and disease: Modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk",
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.",
keywords = "Branching morphogenesis, Semaphorin3a, Semaphorin3c, Vascular patterning",
author = "Reidy, {Kimberly J.} and Alda Tufro",
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AU - Tufro, Alda

PY - 2011/9

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N2 - 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.

AB - 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.

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