Notch Signaling Pathway - Function

Function

The notch signaling pathway is important for cell-cell communication, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Notch signaling also has a role in the following processes:

• neuronal function and development
• stabilization of arterial endothelial fate and angiogenesis
• regulation of crucial cell communication events between endocardium and myocardium during both the formation of the valve primordial and ventricular development and differentiation
• cardiac valve homeostasis, as well as implications in other human disorders involving the cardiovascular system
• timely cell lineage specification of both endocrine and exocrine pancreas
• influencing of binary fate decisions of cells that must choose between the secretory and absorptive lineages in the gut
• expansion of the hematopoietic stem cell compartment during bone development and participation in commitment to the osteoblastic lineage, suggesting a potential therapeutic role for notch in bone regeneration and osteoporosis
• T cell lineage commitment from common lymphoid precursor
• regulation of cell-fate decision in mammary glands at several distinct development stages
• possibly some non-nuclear mechanisms, such as control of the actin cytoskeleton through the tyrosine kinase Abl

Notch signaling is dysregulated in many cancers, and faulty notch signaling is implicated in many diseases including T-ALL (T-cell acute lymphoblastic leukemia), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), MS (Multiple Sclerosis), Tetralogy of Fallot, Alagille syndrome, and many other disease states.

Inhibition of notch signaling has been shown to have anti-proliferative effects on T-cell acute lymphoblastic leukemia in cultured cells and in a mouse model. It has also been found that Rex1 has inhibitory effects on the expression of notch in mesenchymal stem cells, preventing differentiation.