<P> Notch signaling is known to occur inside ciliated, differentiating cells found in the first epidermal layers during early skin development . Furthermore, it has found that presenilin - 2 works in conjunction with ARF4 to regulate Notch signaling during this development . However, it remains to determined whether gamma - secretase has a direct or indirect role in modulating Notch signaling . </P> <P> Early findings on Notch signaling in Central Nervous System (CNS) development were performed mainly in Drosophila with mutagenesis experiments . For example, the finding that an embryonic lethal phenotype in Drosophila was associated with Notch dysfunction indicated that Notch mutations can lead to the failure of neural and Epidermal cell segregation in early Drosophila embryos . In the past decade, advances in mutation and knockout techniques allowed research on the Notch signaling pathway in mammalian models, especially rodents . </P> <P> The Notch signaling pathway was found to be critical mainly for neural progenitor cell (NPC) maintenance and self - renewal . In recent years, other functions of the Notch pathway have also been found, including glial cell specification, neurites development, as well as learning and memory . </P> <P> The Notch pathway is essential for maintaining NPCs in the developing brain . Activation of the pathway is sufficient to maintain NPCs in a proliferating state, whereas loss - of - function mutations in the critical components of the pathway cause precocious neuronal differentiation and NPC depletion . Modulators of the Notch signal, e.g., the Numb protein are able to antagonize Notch effects, resulting in the halting of cell cycle and differentiation of NPCs . Conversely, the Fibroblast Growth Factor pathway promotes Notch signaling to keep stem cells of the cerebral cortex in the proliferative state, amounting to a mechanism regulating cortical surface area growth and, potentially, gyrification . In this way, Notch signaling controls NPC self - renewal as well as cell fate specification . </P>

How is it possible that notch cleavage results in two very distinct cell fates