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Notch pathway plays diverse and fundamental roles during animal development. One of the most relevant, which arises directly from its unique mode of activation, is the specification of cell fates and tissue boundaries. The development of the leg of Drosophila melanogaster is a fine example of this Notch function, as it is required to specify the fate of the cells that will eventually form the leg joints, the flexible structures that separate the different segments of the adult leg. Notch activity is accurately activated and maintained at the distal end of each segment in response to the proximo-distal patterning gene network of the developing leg. Region-specific downstream targets of Notch in turn regulate the formation of the different types of joints. We discuss recent findings that shed light on the molecular and cellular mechanisms that are ultimately governed by Notch to achieve epithelial fold and joint morphogenesis. Finally, we briefly summarize the role that Notch plays in inducing the nonautonomous growth of the leg. Overall, this book chapter aims to highlight leg development as a useful model to study how patterning information is translated into specific cell behaviors that shape the final form of an adult organ.Notch signaling is required for maintaining neural stem cells (NSCs) in the developing brain. NSCs have potential to give rise to many neuronal types in the early telencephalon, and the potential decreases as embryonic development proceeds. Nepro, which encodes a unique nucleolar protein and is activated downstream of Notch, is essential for maintaining NSCs in the early telencephalon. Nepro is also expressed at basal levels and required for maintaining the preimplantation embryo, by repressing mitochondria-associated p53 apoptotic signaling. Notch signaling also controls dendritic complexity in mitral cells, major projection neurons in the olfactory bulb, showing that many steps of neural development involve Notch signaling.Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt-and-pepper pattern formation during various biological processes. In many cases, Notch signaling acts together with other signaling systems. However, it is not clear what happens when Notch signaling is combined with other signaling systems. Mathematical modeling and the use of a simple biological model system will be essential to address this uncertainty. A wave of differentiation in the Drosophila visual center, the "proneural wave," accompanies the activity of the Notch and EGF signaling pathways. Although all of the Notch signaling components required for lateral inhibition are involved in the proneural wave, no salt-and-pepper pattern is found during the progression of the proneural wave. Instead, Notch is activated along the wave front and regulates proneural wave progression. How does Notch signaling control wave propagation without forming a salt-and-pepper pattern? A mathematical model of the proneural wave, based on biological evidence, has demonstrated that Notch-mediated lateral inhibition is implemented within the proneural wave and that the diffusible action of EGF cancels salt-and-pepper pattern formation. The results from numerical simulation have been confirmed by genetic experiments in vivo and suggest that the combination of Notch-mediated lateral inhibition and EGF-mediated reaction diffusion enables a novel function of Notch signaling that regulates propagation of the proneural wave. Similar mechanisms may play important roles in diverse biological processes found in animal development and cancer pathogenesis.Notch signaling exerts multiple important functions in various developmental processes, including cell differentiation and cell proliferation, while mis-regulation of this pathway results in a variety of complex diseases, such as cancer and developmental defects. The simplicity of the Notch pathway in Drosophila melanogaster, in combination with the availability of powerful genetics, makes this an attractive model for studying the fundamental mechanisms of how Notch signaling is regulated and how it functions in various cellular contexts. Recently, increasing evidence for epigenetic control of Notch signaling reveals the intimate link between epigenetic regulators and Notch signaling pathway. In this chapter, we summarize the research advances of Notch and CAF-1 in Drosophila development and the epigenetic regulation mechanisms of Notch signaling activity by CAF-1 as well as other epigenetic modification machineries, which enables Notch to orchestrate different biological inputs and outputs in specific cellular contexts.During central nervous system (CNS) development, a complex series of events play out, starting with the establishment of neural progenitor cells, followed by their asymmetric division and formation of lineages and the differentiation of neurons and glia. Studies in the Drosophila melanogaster embryonic CNS have revealed that the Notch signal transduction pathway plays at least five different and distinct roles during these events. Herein, we review these many faces of Notch signalling and discuss the mechanisms that ensure context-dependent and compartment-dependent signalling. We conclude by discussing some outstanding issues regarding Notch signalling in this system, which likely have bearing on Notch signalling in many species.The evolutionary highly conserved Notch pathway, which first developed during evolution in metazoans and was first discovered in fruit flies (Drosophila melanogaster), governs many core processes including cell fate decisions during embryonic development. A huge mountain of scientific evidence convincingly demonstrates that Notch signaling represents one of the most important pathways that regulate embryogenesis from sponges, roundworms, Drosophila melanogaster, and mice to humans. Inflammation antagonist In this review, we give a brief introduction on how Notch orchestrates the embryonic development of several selected tissues, summarizing some of the most relevant findings in the central nervous system, skin, kidneys, liver, pancreas, inner ear, eye, skeleton, heart, and vascular system.

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