Notch: A multi-functional integrating system of microenvironmental signals

• Published in: Developmental biology Vol. 418; no. 2; pp. 227 - 241
• Main Authors: LaFoya, Bryce, Munroe, Jordan A., Mia, Masum M., Detweiler, Michael A., Crow, Jacob J., Wood, Travis, Roth, Steven, Sharma, Bikram, Albig, Allan R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2016
• Subjects: Animals; Cellular Microenvironment - physiology; Extracellular Matrix - physiology; Humans; Hyperglycemia - physiopathology; Hypoxia - physiopathology; Integrins - physiology; Models, Biological; Receptor Cross-Talk - physiology; Receptors, Notch - physiology; Signal Transduction - physiology; Stress, Physiological - physiology; Transforming Growth Factor beta - physiology; Vascular Endothelial Growth Factor A - physiology; Wnt Signaling Pathway - physiology
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2016.08.023

The Notch signaling cascade is an evolutionarily ancient system that allows cells to interact with their microenvironmental neighbors through direct cell-cell interactions, thereby directing a variety of developmental processes. Recent research is discovering that Notch signaling is also responsive to a broad variety of stimuli beyond cell-cell interactions, including: ECM composition, crosstalk with other signaling systems, shear stress, hypoxia, and hyperglycemia. Given this emerging understanding of Notch responsiveness to microenvironmental conditions, it appears that the classical view of Notch as a mechanism enabling cell-cell interactions, is only a part of a broader function to integrate microenvironmental cues. In this review, we summarize and discuss published data supporting the idea that the full function of Notch signaling is to serve as an integrator of microenvironmental signals thus allowing cells to sense and respond to a multitude of conditions around them. •In addition to adjacent cells, Notch responds to a wide variety of microenvironmental signals.•Notch activation by microenvironmental signals might reflect the evolutionary origins of Notch.•The physiological importance of microenvironmental signal integration by Notch is not fully understood.