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Notch Signaling during Oogenesis in Drosophila melanogaster

DOI: 10.1155/2012/648207

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Abstract:

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance. Discovered and studied initially in Drosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom. In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis in Drosophila. 1. Introduction Utilized by the simplest metazoans through mammals, Notch signaling is an evolutionarily conserved signaling pathway that is required for embryonic development, cell fate specification, and stem cell maintenance [1–5]. Notch signaling selects among preexisting cellular potentials to specify different cell fates and activate different programs through either promoting or suppressing differentiation, proliferation, survival, and apoptosis [6, 7]. In humans, mutations in this pathway cause inherited genetic diseases such as Alagille syndrome, spondylocostal dysostosis, Hadju-Cheney syndrome, Tetralogy of Fallot, familial aortic valve disease, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Dysregulation of Notch activity also is associated with T-cell acute lymphatic leukemia and other cancers (e.g., pancreatic, ovarian, colon, and brain tumors) [3, 8–13]. 2. Notch Receptors and Ligands The Notch gene was discovered by Morgan and colleagues, who observed that X-linked dominant mutations in Drosophila caused irregular notches at the wing margin [14, 15]. Later, Poulson found that the absence of Notch activity in the embryo resulted in the overproduction of neural tissue at the expense of epidermal tissue [16]. This phenotype was termed neurogenic and was later shown to be a characteristic phenotype of several other Drosophila mutants. This defined the Drosophila Notch pathway as a cascade of neurogenic genes that control the formation of the fly nervous system [17]. However, Notch mutants also exhibit several other defects in embryonic and adult tissues, which indicates that this pathway is involved not only in the development of the nervous system but also in cell fate decisions. Today, with subsequent identification of orthologs for Notch in Caenorhabditis elegans and higher vertebrates [18–20], it has been shown that the Notch pathway regulates cell fate decisions, affecting almost all cells of complex animal tissues for proper final differentiation. One Notch receptor gene exists in

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