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.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Reidy
authors.forename: Alda
authors.initials: A
authors.lastname: Tufro
mesh_terms: D000818:Animals; D002450:Cell Communication; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000196:embryology / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D050199:Podocytes / Q000378:metabolism*; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction; D014513:Ureter / Q000196:embryology / Q000378:metabolism*
chemical_list: D040121:Semaphorin-3A