Notch Pathway and Inherited Diseases: Challenge and Promise

  • Jörg ReichrathEmail author
  • Sandra Reichrath
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1218)


The evolutionary highly conserved Notch pathway governs many cellular core processes including cell fate decisions. Although it is characterized by a simple molecular design, Notch signaling, which first developed in metazoans, represents one of the most important pathways that govern embryonic development. Consequently, a broad variety of independent inherited diseases linked to defective Notch signaling has now been identified, including Alagille, Adams-Oliver, and Hajdu-Cheney syndromes, CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), early-onset arteriopathy with cavitating leukodystrophy, lateral meningocele syndrome, and infantile myofibromatosis. In this review, we give a brief overview on molecular pathology and clinical findings in congenital diseases linked to the Notch pathway. Moreover, we discuss future developments in basic science and clinical practice that may emerge from recent progress in our understanding of the role of Notch in health and disease.


Notch Notch signaling Notch pathway Embryonic development Jagged Delta-like ligand 



Autosomal dominant


Alagille syndrome


RhoGTPase-activating protein 31


Bicuspid aortic valve


Bone morphogenetic protein


Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy


Calcific aortic valve disease


Congenital heart disease


Conditional knockout


Central nervous system


Delta-like canonical Notch ligand


Dedicator of cytokinesis


Embryonic day


Epidermal growth factor


Epithelial-to-mesenchymal transition


N-Ethyl N-nitrosourea


EGF domain-specific O-linked N-acetylglucosamine transferase


Fibroblast growth factor


Hajdu-Cheney syndrome


Hairy and enhancer of split


Hypoplastic left heart syndrome


Infantile myofibromatosis






Lateral meningocele syndrome


Loss of function


Lateral wall


Mesenchymal-to-epithelial transition


Neuroepithelial cells


Notch intracellular domain


Negative regulatory region


Neural stem cells


Online Mendelian Inheritance in Man

PEST sequence

Peptide sequence that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T)


Recombination signal binding protein for immunoglobulin kappa J region


Thoracic aortic aneurysms


Tetralogy of Fallot


Ventricular septal defect


Vascular smooth muscle cell




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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of DermatologyThe Saarland University HospitalHomburgGermany

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