Notch signaling in human development and disease.
Mutations in Notch signaling pathway members cause developmental phenotypes that affect the liver, skeleton, heart, eye, face, kidney, and vasculature. Notch associated disorders include the autosomal dominant, multi-system, Alagille syndrome caused by mutations in both a ligand (Jagged1 (JAG1)) and receptor (NOTCH2) and autosomal recessive spondylocostal dysostosis, caused by mutations in a ligand (Delta-like-3 (DLL3)), as well as several other members of the Notch signaling pathway. Mutations in NOTCH2 have also recently been connected to Hajdu-Cheney syndrome, a dominant disorder causing focal bone destruction, osteoporosis, craniofacial morphology and renal cysts. Mutations in the NOTCH1 receptor are associated with several types of cardiac disease and mutations in NOTCH3 cause the dominant adult onset disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a vascular disorder with onset in the 4th or 5th decades. Studies of these human disorders and their inheritance patterns and types of mutations reveal insights into the mechanisms of Notch signaling.
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA.
Andrea L
AL
Penton
Laura D
LD
Leonard
Nancy B
NB
Spinner
D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D016738:Alagille Syndrome / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D031845:Hajdu-Cheney Syndrome / Q000235:genetics / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism; D006548:Hernia, Diaphragmatic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins