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Notch Pathway and Inherited Diseases: Challenge and Promise

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

Abstract

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.

Keywords

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

Abbreviations

AD

Autosomal dominant

ALGS

Alagille syndrome

ARHGAP31

RhoGTPase-activating protein 31

BAV

Bicuspid aortic valve

BMP

Bone morphogenetic protein

CADASIL

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CAVD

Calcific aortic valve disease

CHD

Congenital heart disease

cKO

Conditional knockout

CNS

Central nervous system

Dll

Delta-like canonical Notch ligand

DOCK

Dedicator of cytokinesis

E

Embryonic day

EGF

Epidermal growth factor

EMT

Epithelial-to-mesenchymal transition

ENU

N-Ethyl N-nitrosourea

EOGT

EGF domain-specific O-linked N-acetylglucosamine transferase

FGF

Fibroblast growth factor

HCS

Hajdu-Cheney syndrome

Hes

Hairy and enhancer of split

HLHS

Hypoplastic left heart syndrome

IM

Infantile myofibromatosis

Jag

Jagged

KO

Knockout

LMS

Lateral meningocele syndrome

LOF

Loss of function

LW

Lateral wall

MET

Mesenchymal-to-epithelial transition

NEPs

Neuroepithelial cells

NICD

Notch intracellular domain

NRR

Negative regulatory region

NSCs

Neural stem cells

OMIM

Online Mendelian Inheritance in Man

PEST sequence

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

RBPJ

Recombination signal binding protein for immunoglobulin kappa J region

TAA

Thoracic aortic aneurysms

TOF

Tetralogy of Fallot

VSD

Ventricular septal defect

vSMC

Vascular smooth muscle cell

Wnt

Wingless

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of DermatologyThe Saarland University HospitalHomburgGermany

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