Notch signaling in kidney development.
OBJECTIVE
Notch signaling is a highly conserved mechanism used by multicellular animals to specify cell fate decisions during the formation of complex structures such as the kidney. A number of studies have recently identified requirements for Notch signaling during kidney organogenesis and tissue repair. This review will summarize these studies and compare Notch signaling in the mammalian kidney with Notch signaling in other organ systems.


RESULTS
A targeted mutation in the mouse Notch2 receptor resulted in kidneys that are devoid of glomerular endothelial and mesangial cells. The mutant epithelial cells of the developing glomerulus have reduced amounts of vascular endothelial growth factor expression, which may be responsible for the lack of vascularization observed in these glomeruli. Notch2 is expressed in the epithelial cells of the developing glomerulus, and a potential ligand, Jagged1 is expressed in the endothelial cells of the glomerulus. Mice simultaneously heterozygous for mutations in both Notch2 and Jagged1 phenocopy the kidney defects seen in mice homozygous for the Notch2 mutation. These doubly heterozygous mice also display liver and heart developmental abnormalities reminiscent of Alagille's syndrome.


CONCLUSIONS
Notch signaling is required for kidney development, and the expression of Notch genes is increased in response to kidney damage. Further studies of Notch signaling will be important in order to understand kidney development and tissue repair.
McCright
Brent
B
Division of Cellular and Gene Therapies, FDA, Center for Biologics Evaluations and Research, Bethesda, MD 20892-4555, USA. mccright@cber.fda.gov
D000818:Animals; D002135:Calcium-Binding Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007668:Kidney / Q000254:growth & development* / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000502:physiology; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497764:NOTCH2 protein, human; C497765:Notch2 protein, mouse; D011506:Proteins; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins