Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues

Zielke, Norman; Korzelius, Jerome; Straaten, Monique van; Bender, Katharina; Schuhknecht, Gregor F.P.; Dutta, Devanjali; Xiang, Jun; Edgar, Bruce A.

doi:10.1016/j.celrep.2014.03.020

Cited by 251 publications

(275 citation statements)

References 51 publications

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“…1B,D,E). To monitor the status of the cell cycle in PSC cells with a bam mutant background, we introduced the FUCCI system into this analysis (Sakaue-Sawano et al, 2008;Zielke et al, 2014). The system revealed that bam loss-of-function enhanced the proliferation status of PSC cells compared with wildtype PSC cells ( Fig.…”

Section: Results and Discussion Bam Expression And Function In Lymph mentioning

confidence: 99%

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Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Tokusumi

Hopkins

et al. 2015

Development

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Bag of Marbles (Bam) is known to function as a positive regulator of hematopoietic progenitor maintenance in the lymph gland blood cell-forming organ during Drosophila hematopoiesis. Here, we demonstrate a key function for Bam in cells of the lymph gland posterior signaling center (PSC), a cellular domain proven to function as a hematopoietic niche. Bam is expressed in PSC cells, and gene loss-of-function results in PSC overgrowth and disorganization, indicating that Bam plays a crucial role in controlling the proper development of the niche. It was previously shown that Insulin receptor (InR) pathway signaling is essential for proper PSC cell proliferation. We analyzed PSC cell number in lymph glands double-mutant for bam and InR pathway genes, and observed that bam genetically interacts with pathway members in the formation of a normal PSC. The elF4A protein is a translation factor downstream of InR pathway signaling, and functional knockdown of this crucial regulator rescued the bam PSC overgrowth phenotype, further supporting the cooperative function of Bam with InR pathway members. Additionally, we documented that the Retinoblastoma-family protein (Rbf), a proven regulator of cell proliferation, was present in cells of the PSC, with a bam functiondependent expression. By contrast, perturbation of Decapentaplegic or Wingless signaling failed to affect Rbf niche cell expression. Together, these findings indicate that InR pathway-Bam-Rbf functional interactions represent a newly identified means to regulate the correct size and organization of the PSC hematopoietic niche.

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Section: Results and Discussion Bam Expression And Function In Lymph mentioning

confidence: 99%

“…To monitor cell cycle status of PSC cells in various genetic backgrounds, the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) for Drosophila (FlyFUCCI) system was used (Sakaue-Sawano et al, 2008;Zielke et al, 2014). See supplementary material for fly stocks used.…”

Section: Cell Cycle Monitoringmentioning

confidence: 99%

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Tokusumi

Hopkins

et al. 2015

Development

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“…Our analysis indicates that >95% of Pros + cells express one or more distinct neuropeptides. We predict that the remaining ∼5% of Pros + cells correspond either to newly formed endocrine cells in the process of differentiating, dividing progenitors (see Biteau and Jasper, 2014;Zielke et al, 2014) or differentiated endocrine cells expressing peptides other than those tested.…”

Section: Organization Of the Adult Enteroendocrine Systemmentioning

confidence: 99%

Generation of enteroendocrine cell diversity in midgut stem cell lineages

Beehler-Evans

Micchelli

2015

Development

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The endocrine system mediates long-range peptide hormone signaling to broadcast changes in metabolic status to distant target tissues via the circulatory system. In many animals, the diffuse endocrine system of the gut is the largest endocrine tissue, with the full spectrum of endocrine cell subtypes not yet fully characterized. Here, we combine molecular mapping, lineage tracing and genetic analysis in the adult fruit fly to gain new insight into the cellular and molecular mechanisms governing enteroendocrine cell diversity. Neuropeptide hormone distribution was used as a basis to generate a high-resolution cellular map of the diffuse endocrine system. Our studies show that cell diversity is seen at two distinct levels: regional and local. We find that class I and class II enteroendocrine cells can be distinguished locally by combinatorial expression of secreted neuropeptide hormones. Cell lineage tracing studies demonstrate that class I and class II cells arise from a common stem cell lineage and that peptide profiles are a stable feature of enteroendocrine cell identity during homeostasis and following challenge with the enteric pathogen Pseudomonas entomophila. Genetic analysis shows that Notch signaling controls the establishment of class II cells in the lineage, but is insufficient to reprogram extant class I cells into class II enteroendocrine cells. Thus, one mechanism by which secretory cell diversity is achieved in the diffuse endocrine system is through cellcell signaling interactions within individual adult stem cell lineages.

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“…In the Drosophila midgut, the ISCs give rise to two types of daughter progenitors, the undifferentiated enteroblast (EB) and the preenteroendocrine ( pre-EE) cell (Beehler-Evans and Micchelli, 2015;Biteau and Jasper, 2014;Micchelli and Perrimon, 2006;Ohlstein and Spradling, 2006;Zeng and Hou, 2015;Zielke et al, 2014). EBs and pre-EEs differentiate into absorptive enterocytes (ECs) and secretory enteroendocrine (EE) cells, respectively.…”

Section: Tnks Is Essential For Control Of Isc Proliferation In the Admentioning

confidence: 99%

The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis in Drosophila

et al. 2016

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Wnt/β-catenin signaling controls intestinal stem cell (ISC) proliferation, and is aberrantly activated in colorectal cancer. Inhibitors of the ADP-ribose polymerase Tankyrase (Tnks) have become lead therapeutic candidates for Wnt-driven cancers, following the recent discovery that Tnks targets Axin, a negative regulator of Wnt signaling, for proteolysis. Initial reports indicated that Tnks is important for Wnt pathway activation in cultured human cell lines. However, the requirement for Tnks in physiological settings has been less clear, as subsequent studies in mice, fish and flies suggested that Tnks was either entirely dispensable for Wntdependent processes in vivo, or alternatively, had tissue-specific roles. Here, using null alleles, we demonstrate that the regulation of Axin by the highly conserved Drosophila Tnks homolog is essential for the control of ISC proliferation. Furthermore, in the adult intestine, where activity of the Wingless pathway is graded and peaks at each compartmental boundary, Tnks is dispensable for signaling in regions where pathway activity is high, but essential where pathway activity is relatively low. Finally, as observed previously for Wingless pathway components, Tnks activity in absorptive enterocytes controls the proliferation of neighboring ISCs non-autonomously by regulating JAK/STAT signaling. These findings reveal the requirement for Tnks in the control of ISC proliferation and suggest an essential role in the amplification of Wnt signaling, with relevance for development, homeostasis and cancer.

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Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues

Cited by 251 publications

References 51 publications

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Generation of enteroendocrine cell diversity in midgut stem cell lineages

The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis in Drosophila

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