Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways

Fu, Ziwen; Geng, Cuiyun; Wang, Hui; Yang, Zinger; Weng, Changjiang; Li, Hua; Deng, Lüe; Liu, Luping; Liu, Nan; Ni, Jian-Quan; Xie, Ting

doi:10.1016/j.celrep.2015.10.017

Cited by 32 publications

(30 citation statements)

References 56 publications

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“…Thus, one possible model is that Bam/Otu creates an intrinsic timer in dividing cysts by stabilizing CycA in cystoblasts and 2-cell cysts, promoting subsequent APC/C activity and destruction of CycA in 4and 8-cell cysts, triggering the terminal mitotic division. The Bam/Otu timer could be reinforced by other mechanisms that either activate the APC/C, such as Gcn5-induced acetylation , or regulate CycA levels, such as reduction of CycA mRNA by the CCR4-NOT deadenylase complex (Morris et al, 2005;Fu et al, 2015;Sgromo et al, 2018) and the translational repressor Bruno (Sugimura and Lilly, 2006).…”

Section: An Intrinsic Timer Likely Regulates Fusome-orchestrated Mitomentioning

confidence: 99%

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Hinnant

Merkle

Ables

2020

Front. Cell Dev. Biol.

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Gametes are highly specialized cell types produced by a complex differentiation process. Production of viable oocytes requires a series of precise and coordinated molecular events. Early in their development, germ cells are an interconnected group of mitotically dividing cells. Key regulatory events lead to the specification of mature oocytes and initiate a switch to the meiotic cell cycle program. Though the chromosomal events of meiosis have been extensively studied, it is unclear how other aspects of oocyte specification are temporally coordinated. The fruit fly, Drosophila melanogaster, has long been at the forefront as a model system for genetics and cell biology research. The adult Drosophila ovary continuously produces germ cells throughout the organism's lifetime, and many of the cellular processes that occur to establish oocyte fate are conserved with mammalian gamete development. Here, we review recent discoveries from Drosophila that advance our understanding of how early germ cells balance mitotic exit with meiotic initiation. We discuss cell cycle control and establishment of cell polarity as major themes in oocyte specification. We also highlight a germline-specific organelle, the fusome, as integral to the coordination of cell division, cell polarity, and cell fate in ovarian germ cells. Finally, we discuss how the molecular controls of the cell cycle might be integrated with cell polarity and cell fate to maintain oocyte production.

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Section: An Intrinsic Timer Likely Regulates Fusome-orchestrated Mitomentioning

confidence: 99%

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Hinnant

Merkle

Ables

2020

Front. Cell Dev. Biol.

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“…Bam works with Smurf to repress BMP signaling in GSC progeny by unknown mechanisms (Casanueva and Ferguson, 2004). Bam can also inactivate or convert the selfrenewal functions of the translation initiation eIF4 complex, the deadenylase CCR4-NOT complex and the COP9 signalosome complex by directly binding to one component of these complexes, eIF-4A, CSN4 and Twin, respectively (Fu et al, 2015;Pan et al, 2014;Shen et al, 2009). Therefore, Bam controls GSC progeny differentiation via multiple independent mechanisms.…”

Section: Introductionmentioning

confidence: 99%

DNA damage-induced Lok/CHK2 activation compromises germline stem cell self-renewal and lineage differentiation

Han

Song

et al. 2016

Development

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Stem cells in adult tissues are constantly exposed to genotoxic stress and also accumulate DNA damage with age. However, it remains largely unknown how DNA damage affects both stem cell selfrenewal and differentiation. In this study, we show that DNA damage retards germline stem cell (GSC) self-renewal and progeny differentiation in a Lok kinase-dependent manner in the Drosophila ovary. Both heatshock-inducible endonuclease I-CreI expression and X-ray irradiation can efficiently introduce double-strand breaks in GSCs and their progeny, resulting in a rapid GSC loss and a GSC progeny differentiation defect. Surprisingly, the elimination of Lok or its kinase activity can almost fully rescue the GSC loss and the progeny differentiation defect caused by DNA damage induced by I-CreI or X-ray. In addition, the reduction in bone morphogenetic protein signaling and Shotgun expression only makes a limited contribution to DNA damage-induced GSC loss. Finally, DNA damage also decreases the expression of the master differentiation factor Bam in a Lok-dependent manner, which helps explain the GSC progeny differentiation defect. Therefore, this study demonstrates, for the first time in vivo, that Lok kinase activation is required for the DNA damage-mediated disruption of adult stem cell self-renewal and lineage differentiation, and might also offer novel insight into how DNA damage causes tissue aging and cancer formation.

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“…Whether Het‐A repression does contribute to CCR4 function in GSC self‐renewal, in addition to its major role in mRNA regulation, remains unknown. The twin GSC loss phenotype was reported to be partially rescued upon Chk2 downregulation using RNAi; however, the rescue was not robust and would require validation using mutants (Fu et al , ).…”

Section: Discussionmentioning

confidence: 99%

Aubergine and pi RNA s promote germline stem cell self‐renewal by repressing the proto‐oncogene Cbl

et al. 2017

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PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self‐renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self‐renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self‐renewal and acts through direct mRNA regulation. We identify the Cbl proto‐oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self‐renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4‐NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post‐transcriptional regulators in key developmental decisions.

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Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways

Cited by 32 publications

References 56 publications

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline

DNA damage-induced Lok/CHK2 activation compromises germline stem cell self-renewal and lineage differentiation

Aubergine and pi RNA s promote germline stem cell self‐renewal by repressing the proto‐oncogene Cbl

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