@article{26105821d57d42ceb2e34a60d16eea5f,
title = "The Master Switch Gene Sex-lethal Promotes Female Development by Negatively Regulating the N-Signaling Pathway",
abstract = "Notch (N) signaling is used for cell-fate determination in many different developmental contexts. Here, we show that the master control gene for sex determination in Drosophila melanogaster, Sex-lethal (Sxl), negatively regulates the N-signaling pathway in females. In genetic assays, reducing Sxl activity suppresses the phenotypic effects of N mutations, while increasing Sxl activity enhances the effects. Sxl appears to negatively regulate the pathway by reducing N protein accumulation, and higher levels of N are found in Sxl- clones than in adjacent wild-type cells. The inhibition of N expression does not depend on the known downstream targets of Sxl; however, we find that Sxl protein can bind to N mRNAs. Finally, our results indicate that downregulation of the N pathway by Sxl contributes to sex-specific differences in morphology and suggest that it may also play an important role in follicle cell specification during oogenesis.",
keywords = "DEVBIO",
author = "Penn, {Jill K.M.} and Paul Schedl",
note = "Funding Information: Since the ovary is only present in females the developmental context for Sxl-N regulatory interactions is different from most other tissues in the fly. Like the wing and sternites, Sxl negatively regulates N in the ovarian follicular epithelium. When Sxl activity is lost in follicle cells, we observe a variety of defects in the development of this epithelium, including egg-chamber packaging defects, ectopic polar cells, and extra-long interfollicular stalks. This spectrum of phenotypes closely resembles those seen when there is excess N activity and argues that N must be inappropriately upregulated in the follicular epithelium when Sxl is lost. Consistent with this suggestion, elevated levels of N protein are found in Sxl clones. With the possible caveat that the MSL dosage compensation system is likely activated in the absence of Sxl and thus probably contributes to the upregulation of N protein, these observations suggest that Sxl plays an important role in mediating N specification of cell fate as the follicular epithelium develops. This view is supported by the reciprocal patterns of N and Sxl protein accumulation in the germarium of wild-type females. We find that follicle cells expressing high levels of N in the germarium have only little cytoplasmic Sxl, while lower levels of N are found in follicle cells that have high amounts of cytoplasmic Sxl. If, as we suspect, Sxl regulates N at the level of translation, the turnover of cytoplasmic Sxl and/or its relocalization to the nucleus would be expected to lead to the upregulation of N protein expression. Conversely, in cells that retain abundant cytoplasmic Sxl, N expression should remain repressed. Since the cells in the germarium that are induced to express high levels of N are thought to be the progenitors of the stalk and polar cells, releasing N mRNA from translation inhibition by Sxl would be expected to facilitate the specification of these cell types by the N -signaling pathway. ",
year = "2007",
month = feb,
doi = "10.1016/j.devcel.2007.01.009",
language = "English (US)",
volume = "12",
pages = "275--286",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "2",
}