Abstract
AbstractThe Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.
Highlights
A wide range of cellular functions including cell proliferation, cell survival and cell fate commitment has been shown to be regulated by the activity of Notch signalling in most multicellular organisms [1,2,3,4]
As cells emerge from the morphogenetic furrow (MF), Dl activates to the Notch receptor to promote G1/S progression in all cells, only uncommitted cells enter S-phase in the second mitotic wave (SMW), since Epidermal growth factor receptor (EGFR) activity blocks the cell cycle progression in G1 in the cells that are part of the precluster [72,73,83]
As we have described in this review, these pathways are functionally related to Notch signalling in the control of cell proliferation during normal development [6,8]
Summary
A wide range of cellular functions including cell proliferation, cell survival and cell fate commitment has been shown to be regulated by the activity of Notch signalling in most multicellular organisms [1,2,3,4] With these pleiotropic effects, there is extensive evidence linking the deregulation of Notch pathway with multiple diseases and cancer [4,5,6,7,8]. Numerous studies have highlighted the power of using the development of the Drosophila imaginal discs as an in vivo system model for analyzing how cooperative interactions between t h e Notch pathway and other signals contribute to regulate cell proliferation in epithelia These structures have been employed to define the molecular mechanisms underlying tumor development and metastasis when Notch signalling is perturbed [10]. The mechanisms of normal Notch signalling regulating cell proliferation may provide useful insights to understand how alteration in this pathway can induce tumorogenesis
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