Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis

Dobens, Leonard L.; Jaeger, Amy; Peterson, Jeanne S.; Raftery, Laurel A.

doi:10.1016/j.ydbio.2005.09.019

Cited by 39 publications

(48 citation statements)

References 97 publications

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“…In the Drosophila ovary, it was first shown to be required for maintaining follicle cells in their precursor stage and for specification of polar cells that mark the ends of the egg chamber (Grammont and Irvine, 2001;Larkin et al, 1996;Xu et al, 1992). During late oogenesis, N signaling is required for the switch from the mitotic cycle to the endocycle and differentiation of follicle cells by negatively regulating the cut gene (Shcherbata et al, 2004;Sun and Deng, 2005), and it is also required for patterning the anterior egg shell (Dobens et al, 2005). In this study, we have shown, for the first time to our knowledge, that N signaling is necessary and sufficient for controlling formation of the GSC niche.…”

Section: Introductionmentioning

confidence: 55%

Notch signaling controls germline stem cell niche formation in theDrosophilaovary

et al. 2007

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Stem cells, which can self-renew and generate differentiated cells, have been shown to be controlled by surrounding microenvironments or niches in several adult tissues. However, it remains largely unknown what constitutes a functional niche and how niche formation is controlled. In the Drosophila ovary, germline stem cells (GSCs), which are adjacent to cap cells and two other cell types, have been shown to be maintained in the niche. In this study, we show that Notch signaling controls formation and maintenance of the GSC niche and that cap cells help determine the niche size in the Drosophila ovary. Expanded Notch activation causes the formation of more cap cells and bigger niches, which support more GSCs, whereas compromising Notch signaling during niche formation decreases the cap cell number and niche size and consequently the GSC number. Furthermore, the niches located away from their normal location can still sufficiently sustain GSC self-renewal by maintaining high local BMP signaling and repressing bam as in normal GSCs. Finally, loss of Notch function in adults results in rapid loss of the GSC niche, including cap cells and thus GSCs. Our results indicate that Notch signaling is important for formation and maintenance of the GSC niche, and that cap cells help determine niche size and function.

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Section: Introductionmentioning

confidence: 55%

Notch signaling controls germline stem cell niche formation in theDrosophilaovary

et al. 2007

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“…Notch activation is strongly detected in larval terminal filament and cap cells and is also detected in adult cap cells (17,18). We examined Notch signaling in dinr mutants using the E(spl)m␤-CD2 reporter (17,19) (Fig. 5A-F).…”

Section: Resultsmentioning

confidence: 99%

“…hh-lacZ, a transgene carrying the hedgehog promoter upstream of the bacterial lacZ gene, was used to label terminal filament and cap cells (33). The tubulin-GPH (15), Dad-LacZ (24), and E(spl)m␤-CD2 (17,19) reporters were used to monitor insulin, BMP, and Notch signaling, respectively. The hsflipase (FLP) strain and other genetic elements used are described in Flybase (http://flybase.bio.indiana.edu).…”

Section: Methodsmentioning

confidence: 99%

Insulin levels control female germline stem cell maintenance via the niche in Drosophila

Hsu

Drummond‐Barbosa

2009

Proc. Natl. Acad. Sci. U.S.A.

221

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Stem cell maintenance depends on local signals provided by specialized microenvironments, or niches, in which they reside. The potential role of systemic factors in stem cell maintenance, however, has remained largely unexplored. Here, we show that insulin signaling integrates the effects of diet and age on germline stem cell (GSC) maintenance through the dual regulation of cap cell number (via Notch signaling) and cap cell-GSC interaction (via E-cadherin) and that the normal process of GSC and niche cell loss that occurs with age can be suppressed by increased levels of insulin-like peptides. These results underscore the importance of systemic factors for the regulation of stem cell niches and, thereby, of stem cell numbers.diet ͉ oogenesis ͉ Notch ͉ E-cadherin ͉ aging T he stem cell microenvironment (niche) controls stem cells (1, 2), and niche aging leads to stem cell decline (3-5). The Drosophila germline stem cell (GSC) niche includes terminal filament cells, cap cells, and escort stem cells, and GSC fate and activity require direct contact with cap cells and exposure to niche-derived signals (6). GSCs also respond to systemic signals, such as Drosophila insulin-like peptides (DILPs) (7,8), which directly modulate their proliferation (9). Increased age leads to decreased niche size and signaling and GSC loss (3). The molecular basis for age-dependent changes in the niche, however, remains poorly understood. Results and DiscussionBecause diet influences aging (10), we examined its effects on GSC maintenance, exploiting the fact that GSCs can be unambiguously identified by their anteriorly anchored fusome (a membranous cytoskeletal structure) and by their juxtaposition to cap cells (11). As previously reported (3, 11, 12), we also observed a decrease in GSC numbers in well-fed females over time. In females on a poor diet, however, the rate of GSC loss was significantly increased (Fig. 1 A, B, and E and supporting information (SI) Table S1).Insulin secretion and signaling respond to diet (13) and diminish in aging humans (14). Using a phosphoinositide 3-kinase reporter (15), we found reduced insulin signaling in older ovaries (Fig. S1). To address if GSC maintenance requires insulin signaling, we measured GSC numbers in Drosophila insulin receptor (dinr) mutants (Fig. 1 C-E and Table S1). The dinr 339 /dinr E19 females contain slightly fewer GSCs at eclosion and lose them significantly faster than controls. We did not detect GSC death in dinr 339 /dinr E19 (n ϭ 65) or control (n ϭ 15) germaria, suggesting that GSC loss results from differentiation. The chico 1 homozygotes, which lack insulin receptor substrate, a major insulin pathway component, also show increased GSC loss (Table S1). Thus, insulin signaling controls GSC maintenance.We next tested if DILP expression in germarial somatic cells could counteract the wild-type age-dependent GSC loss. We used the c587-GAL4 driver (see Materials and Methods) to express a UAS-dilp2 transgene, encoding the DILP most closely related to human insulin (16), and thereby ...

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“…36). These alleles provided a unique opportunity to investigate the function of TDB large isoforms in the follicular epithelium, where we know the most about bun functions (23,24). Expression of the large A isoform alone rescues null and heteroallelic mutations, suggesting that the small isoforms may be dispensable (36).…”

Section: Resultsmentioning

confidence: 99%

“…We have studied bun function in the follicular epithelium that overlies each maturing oocyte. Here, bun prevents epithelial cells from being recruited to a migratory fate (23); the boundary between epithelial and migrating cells is regulated through EGF and BMP regulation of bun expression (24). Expression of vertebrate TSC22D1 is similarly up-regulated by receptor tyrosine kinase signaling and down-regulated by BMP signaling during initiation of feather bud outgrowth in chicken skin (25).…”

mentioning

confidence: 99%

The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival

Wu¹,

Yamada-Mabuchi²,

Morris

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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TSC22D1, which encodes transforming growth factor ␤-stimulated clone 22 (TSC-22), is thought to be a tumor suppressor because its expression is lost in many glioblastoma, salivary gland, and prostate cancers. TSC-22 is the founding member of the TSC-22/DIP/Bun family of leucine zipper transcription factors; its functions have not been investigated in a multicellular environment. Genetic studies in the model organism Drosophila melanogaster often provide fundamental insights into mechanisms disrupted in carcinogenesis, because of the strong evolutionary conservation of molecular mechanisms between flies and humans. Whereas humans and mice have four TSC-22 domain genes with numerous isoforms, Drosophila has only one TSC-22 domain gene, bunched (bun), which encodes both large and small protein isoforms. Surprisingly, Drosophila Bun proteins promote cellular growth and proliferation in ovarian follicle cells. Loss of both large isoforms has the strongest phenotypes, including increased apoptosis. Cultured S2 cells depleted for large Bun isoforms show increased apoptosis and less frequent cell division, with decreased cell size. Altogether, these data indicate that Drosophila TSC-22/DIP/Bun proteins are necessary for cellular growth, proliferation, and survival both in culture and in an epithelial context. Previous work demonstrated that bun prevents recruitment of epithelial cells to a migratory fate and, thus, maintains epithelial organization. We speculate that reduced TSC22D1 expression generally reduces cellular fitness and only contributes to carcinogenesis in specific tissue environments. The strong conservation of genes and molecular mechanisms between flies and humans makes this an ideal organism to evaluate candidate tumor-suppressor functions in vivo.

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Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis

Cited by 39 publications

References 97 publications

Notch signaling controls germline stem cell niche formation in theDrosophilaovary

Notch signaling controls germline stem cell niche formation in theDrosophilaovary

Insulin levels control female germline stem cell maintenance via the niche in Drosophila

The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival

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