A role for the Drosophila bag-of-marbles protein in the differentiation of cystoblasts from germline stem cells

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2937-2947 ◽  
Author(s):  
D. McKearin ◽  
B. Ohlstein

Cell differentiation commonly dictates a change in the cell cycle of mitotic daughters. Previous investigations have suggested that the Drosophila bag of marbles (bam) gene is required for the differentiation of germline stem cell daughters (cystoblasts) from the mother stem cells, perhaps by altering the cell cycle. In this paper, we report the preparation of antibodies to the Bam protein and the use of those reagents to investigate how Bam is required for germ cell development. We find that Bam exists as both a fusome component and as cytoplasmic protein and that cytoplasmic and fusome Bam might have separable activities. We also show that bam mutant germ cells are blocked in differentiation and are trapped as mitotically active cells like stem cells. A model for how Bam might regulate cystocyte differentiation is presented.

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 679-690 ◽  
Author(s):  
A. Forbes ◽  
R. Lehmann

The zinc-finger protein Nanos and the RNA-binding protein Pumilio act together to repress the translation of maternal hunchback RNA in the posterior of the Drosophila embryo, thereby allowing abdomen formation. nanos RNA is localized to the posterior pole during oogenesis and the posteriorly synthesized Nanos protein is sequestered into the germ cells as they form in the embryo. This maternally provided Nanos protein is present in germ cells throughout embryogenesis. Here we show that maternally deposited Nanos protein is essential for germ cell migration. Lack of zygotic activity of nanos and pumilio has a dramatic effect on germline development of homozygous females. Given the coordinate function of nanos and pumilio in embryonic patterning, we analyzed the role of these genes in oogenesis. We find that both genes act in the germline. Although the nanos and pumilio ovarian phenotypes have similarities and both genes ultimately affect germline stem cell development, the focus of these phenotypes appears to be different. While pumilio mutant ovaries fail to maintain stem cells and all germline cells differentiate into egg chambers, the focus of nanos function seems to lie in the differentiation of the stem cell progeny, the cystoblast. Consistent with the model that nanos and pumilio have different phenotypic foci during oogenesis, we detect high levels of Pumilio protein in the germline stem cells and high levels of Nanos in the dividing cystoblasts. We therefore suggest that, in contrast to embryonic patterning, Nanos and Pumilio may interact with different partners in the germline.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Salvador C Herrera ◽  
Erika A Bach

Exhaustion of stem cells is a hallmark of aging. In the Drosophila testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expressing the differentiation factor bag of marbles (bam) in spermatogonia while lineage-labeling these cells. Strikingly, blocking bam-lineage dedifferentiation under normal conditions in virgin males has no impact on the GSC pool. However, in mated males or challenging conditions, inhibiting bam-lineage dedifferentiation markedly reduces the number of GSCs and their ability to proliferate and differentiate. We find that bam-lineage derived GSCs have significantly higher proliferation rates than sibling GSCs in the same testis. We determined that Jun N-terminal kinase (JNK) activity is autonomously required for bam-lineage dedifferentiation. Overall, we show that dedifferentiation provides a mechanism to maintain the germline and ensure fertility under chronically stressful conditions.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1469
Author(s):  
Changhua Sun ◽  
Kai Jin ◽  
Qisheng Zuo ◽  
Hongyan Sun ◽  
Jiuzhou Song ◽  
...  

Alternative splicing (AS) is a ubiquitous, co-transcriptional, and post-transcriptional regulation mechanism during certain developmental processes, such as germ cell differentiation. A thorough understanding of germ cell differentiation will help us to open new avenues for avian reproduction, stem cell biology, and advances in medicines for human consumption. Here, based on single-cell RNA-seq, we characterized genome-wide AS events in manifold chicken male germ cells: embryonic stem cells (ESCs), gonad primordial germ cells (gPGCs), and spermatogonia stem cells (SSCs). A total of 38,494 AS events from 15,338 genes were detected in ESCs, with a total of 48,955 events from 14,783 genes and 49,900 events from 15,089 genes observed in gPGCs and SSCs, respectively. Moreover, this distribution of AS events suggests the diverse splicing feature of ESCs, gPGCs, and SSCs. Finally, several crucial stage-specific genes, such as NANOG, POU5F3, LIN28B, BMP4, STRA8, and LHX9, were identified in AS events that were transmitted in ESCs, gPGCs, and SSCs. The gene expression results of the RNA-seq data were validated by qRT-PCR. In summary, we provided a comprehensive atlas of the genome-wide scale of the AS event landscape in male chicken germ-line cells and presented its distribution for the first time. This research may someday improve treatment options for men suffering from male infertility.


Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3651-3662 ◽  
Author(s):  
B. Ohlstein ◽  
D. McKearin

The Drosophila germ-cell lineage has emerged as a remarkable system for identifying genes required for changes in cell fate from stem cells into more specialized cells. Previous work indicates that bam expression is necessary for cystoblast differentiation; bam mutant germ cells fail to differentiate, but instead proliferate like stem cells. This paper reports that ectopic expression of bam is sufficient to extinguish stem cell divisions. Heat-induced bam+ expression specifically eliminated oogenic stem cells while somatic stem cell populations were not affected. Together with previous studies of the timing of bam mRNA and protein expression and the state of arrest in bam mutant cells, these data implicate Bam as a direct regulator of the switch from stem cell to cystoblast. Surprisingly, ectopic bam+ had no deleterious consequences for male germline cells suggesting that Bam may regulate somewhat different steps of germ-cell development in oogenesis and spermatogenesis. We discuss a model for how bam+ could direct differentiation based on our data (McKearin and Ohlstein, 1995) that Bam protein is essential to assemble part of the germ-cell-specific organelle, the fusome. We propose that fusome biogenesis is an obligate step for cystoblast cell fate and that Bam is the limiting factor for fusome maturation in female germ cells.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Filippo Artoni ◽  
Rebecca E Kreipke ◽  
Ondina Palmeira ◽  
Connor Dixon ◽  
Zachary Goldberg ◽  
...  

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.


2012 ◽  
Vol 23 (8) ◽  
pp. 1524-1532 ◽  
Author(s):  
Therese M. Roth ◽  
C.-Y. Ason Chiang ◽  
Mayu Inaba ◽  
Hebao Yuan ◽  
Viktoria Salzmann ◽  
...  

Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self-renewal and differentiation. Although asymmetric stem cell division balances between self-renewal and differentiation, it does not dictate how frequently differentiating cells must be produced. In male GSCs, asymmetric GSC division is achieved by stereotyped positioning of the centrosome with respect to the stem cell niche. Recently we showed that the centrosome orientation checkpoint monitors the correct centrosome orientation to ensure an asymmetric outcome of the GSC division. When GSC centrosomes are not correctly oriented with respect to the niche, GSC cell cycle is arrested/delayed until the correct centrosome orientation is reacquired. Here we show that induction of centrosome misorientation upon culture in poor nutrient conditions mediates slowing of GSC cell proliferation via activation of the centrosome orientation checkpoint. Consistently, inactivation of the centrosome orientation checkpoint leads to lack of cell cycle slowdown even under poor nutrient conditions. We propose that centrosome misorientation serves as a mediator that transduces nutrient information into stem cell proliferation, providing a previously unappreciated mechanism of stem cell regulation in response to nutrient conditions.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Zezheng Pan ◽  
Mengli Sun ◽  
Xia Liang ◽  
Jia Li ◽  
Fangyue Zhou ◽  
...  

The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years.


2018 ◽  
Author(s):  
Hannah S. Seidel ◽  
Tilmira A. Smith ◽  
Jessica K. Evans ◽  
Jarred Q. Stamper ◽  
Thomas G. Mast ◽  
...  

AbstractKnowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the ‘progenitor zone’. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described “steps” in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.


2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110294
Author(s):  
Shu-Xin Ma ◽  
Li-Bo Tang ◽  
Zhi-Hang Chen ◽  
Min-Li Wei ◽  
Zi-Juan Tang ◽  
...  

Objective To investigate the effects and potential mechanism of action of shikonin (SHK) on the development of ovarian follicles and female germline stem cells (FGSCs). Methods Female Kunming adult mice were administered SHK (0, 20 and 50 mg/kg) by oral gavage. Cultures of FGSCs were treated with SHK 32 μmol/l for 24 h. The ovarian index in mouse ovaries was calculated. Numbers of primordial, primary and atretic follicles were counted. Germline stem cell markers and apoptosis were examined. Levels of glutathione (GSH), superoxide dismutase (SOD) and reactive oxygen species (ROS) were measured. Results Both doses of SHK significantly decreased the ovarian index, the numbers of primordial follicles, primary follicles and antral follicles in mice. SHK significantly increased the numbers of atretic follicles and atretic corpora lutea. SHK promoted apoptosis in vivo and in vitro. SHK significantly decreased the levels of the germline stem cell markers. SHK significantly lowered GSH levels and the activity of SOD in the peripheral blood from mice, whereas SHK significantly elevated cellular ROS content in FGSCs. Conclusions These current results suggested that follicular development and FGSCs were suppressed by SHK through the induction of apoptosis and oxidative stress might be involved in this pathological process.


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