A Snapshot of the Molecular Biology of Notch Signaling: Challenges and Promises

Abstract

Evolutionary conserved Notch signaling is of high importance for embryogenesis and adult tissues, representing one of the most fascinating pathways that regulate key cell fate decisions and other core processes. This chapter gives a short introduction to the first volume of the book entitled Notch Signaling in Embryology and Cancer, that is intended to provide both basic scientists and clinicians who seek today`s clearest understanding of the molecular mechanisms that mediate Notch signaling with an authoritative day-to-day source. On a first look, Notch signaling, that first developed in metazoans and that was first discovered in a fruit fly, seems fallaciously simple, with its key feature being a direct link between an extracellular signal and transcriptional output without the requirement of an extended chain of protein intermediaries as needed by the majority of other signaling pathways. However, on a second, closer look, this obvious simplicity hides remarkable complexity. Notch signaling, that relies on an extensive collection of mechanisms that it exerts alongside of its core transcriptional machinery, orchestrates and governs cellular development by inducing and regulating communication between adjacent cells. In general, a cell expressing the Notch receptor can be activated in trans by ligands on an adjacent cell leading to alteration of transcription and cellular fate. However, ligands also have the ability to inhibit Notch signaling and this can be accomplished when both receptor and ligands are co-expressed in cis on the same cell. The so called non-canonical Notch pathways further diversify the potential outputs of Notch, and allow it to coordinate regulation of many aspects of cell biology. Fortunately, the generation and investigation of knockout mice and other animal models have in recent years resulted in a huge volume of new scientific informations concerning Notch gene function, allowing to dissect the role of specific Notch components for human development and health, and showing promise in opening new avenues for prevention and therapy of a broad variety of independent diseases, including cancer, although this goal is still challenging.