scholarly journals Nuclear export in somatic cyst cells controls cyst cell-germline coordination and germline differentiation in the Drosophila testis

2018 ◽  
Author(s):  
Fani Papagiannouli ◽  
Margaret T. Fuller ◽  
Ingrid Lohmann
Keyword(s):  
Cell Survival ◽  
Germ Cells ◽  
Nuclear Export ◽  
Cell Function ◽  
Intrinsic Cues ◽  
Cyst Cell ◽  
Germ Cell Differentiation ◽  
Cyst Cells ◽  
Drosophila Testis ◽  
Germline Differentiation

SUMMARYNucleocytoplasmic communication is crucial for proper cell function and coordination of intrinsic cues with signaling responses emanating from the neighboring cells and the local tissue microenvironment. In the Drosophila male germline system, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small cyst, the functional unit of differentiation. Here we show that the peripheral nucleoporins Nup62, Nup214 and Nup88, and the exportin Emb are critically required in cyst cells to maintain cyst cell survival and germline encapsulation in order to protect cyst cell-germline communication and promote germ cell differentiation. Knockdown of nup62, emb, nup214 or nup88 in cyst cells leads to cell-autonomous defects in mRNA export, and cell non-autonomous overproliferation of early germ cells in the absence of cyst cell-derived differentiation signals. Suppression of apoptosis can reverse cyst cell elimination and partially restored those defects. Interestingly, overexpression of the Drosophila Profilin gene chickadee can rescue cyst cell survival and restore germline encapsulation and differentiation, by counteracting Ntf-2 mediated export, suggesting that the function of Profilin in cyst cells is linked to nuclear export.

scholarly journals Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiation†

2020 ◽  
Vol 103 (4) ◽  
pp. 717-735
Author(s):  
Yohei Hayashi ◽  
Masaru Mori ◽  
Kaori Igarashi ◽  
Keiko Tanaka ◽  
Asuka Takehara ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Development ◽  
Nucleotide Synthesis ◽  
Male Germ Cells ◽  
Regulatory Pathways ◽  
Germ Cell Development ◽  
Germ Cell Differentiation ◽  
Germline Differentiation

Abstract Regulatory mechanisms of germline differentiation have generally been explained via the function of signaling pathways, transcription factors, and epigenetic regulation; however, little is known regarding proteomic and metabolomic regulation and their contribution to germ cell development. Here, we conducted integrated proteomic and metabolomic analyses of fetal germ cells in mice on embryonic day (E)13.5 and E18.5 and demonstrate sex- and developmental stage-dependent changes in these processes. In male germ cells, RNA processing, translation, oxidative phosphorylation, and nucleotide synthesis are dominant in E13.5 and then decline until E18.5, which corresponds to the prolonged cell division and more enhanced hyper-transcription/translation in male primordial germ cells and their subsequent repression. Tricarboxylic acid cycle and one-carbon pathway are consistently upregulated in fetal male germ cells, suggesting their involvement in epigenetic changes preceding in males. Increased protein stability and oxidative phosphorylation during female germ cell differentiation suggests an upregulation of aerobic energy metabolism, which likely contributes to the proteostasis required for oocyte maturation in subsequent stages. The features elucidated in this study shed light on the unrevealed mechanisms of germ cell development.

scholarly journals discs large regulates somatic cyst cell survival and expansion in Drosophila testis

Cell Research ◽  
2009 ◽  
Vol 19 (10) ◽  
pp. 1139-1149 ◽  
Author(s):  
Fani Papagiannouli ◽  
Bernard M Mechler
Keyword(s):  
Cell Survival ◽  
Cyst Cell ◽  
Discs Large ◽  
Drosophila Testis ◽  
Somatic Cyst Cell

scholarly journals Stem cells commit to differentiation following multiple induction events in the Drosophila testis.

2021 ◽  
Author(s):  
Marc Amoyel ◽  
Alice C Yuen ◽  
Kenzo-Hugo Hillion
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Intercellular Communication ◽  
Self Renewal ◽  
Tor Pathway ◽  
Daughter Cells ◽  
Cyst Cells ◽  
Drosophila Testis ◽  
Primed State

How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline.

scholarly journals The Dlg-module and clathrin-mediated endocytosis regulate EGFR signaling and cyst cell-germline coordination in the Drosophila testis

2018 ◽  
Author(s):  
Fani Papagiannouli ◽  
Cameron Wynn Berry ◽  
Margaret T. Fuller
Keyword(s):  
Signal Transduction ◽  
Cell Polarity ◽  
Germ Cells ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Egfr Signaling ◽  
Downstream Signaling ◽  
Stem Cell Lineage ◽  
Cyst Cells ◽  
Drosophila Testis

SUMMARYTissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that both the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate EGFR signaling. Knockdown of dlg, scrib, lgl or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides new insights on how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues.

The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2437-2447 ◽  
Author(s):  
P. Gonczy ◽  
S. DiNardo
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cell Fate ◽  
Germ Cells ◽  
Germ Line ◽  
Lineage Tracing ◽  
Somatic Stem Cells ◽  
Daughter Cyst ◽  
Cyst Cell ◽  
Cyst Cells

Spermatogenesis relies on the function of germ-line stem cells, as a continuous supply of differentiated spermatids is produced throughout life. In Drosophila, there must also be somatic stem cells that produce the cyst cells that accompany germ cells throughout spermatogenesis. By lineage tracing, we demonstrate the existence of such somatic stem cells and confirm that of germ-line stem cells. The somatic stem cells likely correspond to the ultrastructurally described cyst progenitor cells. The stem cells for both the germ-line and cyst lineage are anchored around the hub of non-dividing somatic cells located at the testis tip. We then address whether germ cells regulate the behavior of somatic hub cells, cyst progenitors and their daughter cyst cells by analyzing cell proliferation and fate in testes in which the germ line has been genetically ablated. Daughter cyst cells, which normally withdraw from the cell cycle, continue to proliferate in the absence of germ cells. In addition, cells from the cyst lineage switch to the hub cell fate. Male-sterile alleles of chickadee and diaphanous, which are deficient in germ cells, exhibit similar cyst cell phenotypes. We conclude that signaling from germ cells regulates the proliferation and fate of cells in the somatic cyst lineage.

scholarly journals Germ cells commit somatic stem cells to differentiation following priming by PI3K/Tor activity in the Drosophila testis

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009609
Author(s):  
Alice C. Yuen ◽  
Kenzo-Hugo Hillion ◽  
Ruoxu Wang ◽  
Marc Amoyel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Intercellular Communication ◽  
Self Renewal ◽  
Tor Pathway ◽  
Daughter Cells ◽  
Cyst Cells ◽  
Drosophila Testis ◽  
Primed State

How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline.

scholarly journals RNA Kinase CLP1/Cbc Regulates Meiosis Initiation in Spermatogenesis

2021 ◽  
Author(s):  
Wu Jianbo ◽  
Li Xin ◽  
Gao Zhiyang ◽  
Pang Lin ◽  
Liu Xian ◽  
...  
Keyword(s):  
Animal Models ◽  
Subcellular Localization ◽  
Neurodegenerative Diseases ◽  
Germ Cells ◽  
Genetic Manipulations ◽  
Functional Conservation ◽  
Evolutionarily Conserved ◽  
Drosophila Testis ◽  
Germline Differentiation ◽  
Necessary And Sufficient

Abstract CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Stemming from our previous findings on the correlation between mRNA 3′-processing and meiosis entry, here we identify that the RNA kinase Cbc, the Drosophila member of the highly conserved CLP1 family, is a component of the program regulating the transition from mitosis to meiosis. Using genetic manipulations in Drosophila testis, we demonstrate that nuclear Cbc is required to promote meiosis entry. Combining biochemical and genetic methods, we reveal that Cbc physically and/or genetically intersects with Tsen54 and TER94 (VCP ortholog) in this process. The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.

Cell-intrinsic regulation of murine dendritic cell function and survival by prereceptor amplification of glucocorticoid

Blood ◽  
2013 ◽  
Vol 122 (19) ◽  
pp. 3288-3297 ◽  
Author(s):  
Annelise Soulier ◽  
Sandra M. Blois ◽  
Shivajanani Sivakumaran ◽  
Farnaz Fallah-Arani ◽  
Stephen Henderson ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Survival ◽  
Cell Function ◽  
Cell Populations ◽  
Dendritic Cell Function ◽  
Key Points ◽  
Intrinsic Regulation

Key Points Murine dendritic cell populations are highly proficient in amplifying local glucocorticoid concentrations. This property is critical in regulating dendritic cell survival and functions in vivo.

scholarly journals Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. 471-480 ◽  
Author(s):  
Gerardo M Oresti ◽  
Jesús García-López ◽  
Marta I Aveldaño ◽  
Jesús del Mazo
Keyword(s):  
Fatty Acid ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Fatty Acid Binding Proteins ◽  
Cell Type ◽  
Fatty Acid Binding ◽  
Germ Cell Differentiation ◽  
Perilipin 2

Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium.Fabp5expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression ofFabp3increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells.Fabp9, together withFabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressedPlin2. Yet, whileDgat1was detected in Sertoli cells,Dgat2accumulated in germ cells with a similar pattern of expression asFabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age- and germ cell type-associated increases inFabp9,Dgat2, andPlin2levels are thus functionally related in the last stages of germ cell differentiation.

scholarly journals Phase Transitioned Nuclear Oskar Promotes Cell Division of Drosophila Primordial Germ Cells

2018 ◽  
Author(s):  
Kathryn E. Kistler ◽  
Tatjana Trcek ◽  
Thomas R. Hurd ◽  
Ruoyu Chen ◽  
Feng-Xia Liang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Cell Function ◽  
Primordial Germ Cells ◽  
Nuclear Localization Sequence ◽  
Cell Systems ◽  
Germ Granules ◽  
Localization Sequence ◽  
Transcriptional Gene Regulation

ABSTRACTGerm granules are non-membranous ribonucleoprotein granules deemed the hubs for post-transcriptional gene regulation and functionally linked to germ cell fate across species. Little is known about the physical properties of germ granules and how these relate to germ cell function. Here we study two types of germ granules in the Drosophila embryo: cytoplasmic germ granules that instruct primordial germ cells (PGCs) formation and nuclear germ granules within early PGCs with unknown function. We show that cytoplasmic and nuclear germ granules are phase transitioned condensates nucleated by Oskar protein that display liquid as well as hydrogel-like properties. Focusing on nuclear granules, we find that Oskar drives their formation in heterologous cell systems. Multiple, independent Oskar protein domains synergize to promote granule phase separation. Deletion of Oskar’s nuclear localization sequence specifically ablates nuclear granules in cell systems. In the embryo, nuclear germ granules promote germ cell divisions thereby increasing PGC number for the next generation.

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