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.

punt and schnurri regulate a somatically derived signal that restricts proliferation of committed progenitors in the germline

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4383-4391 ◽  
Author(s):  
E. Matunis ◽  
J. Tran ◽  
P. Gonczy ◽  
K. Caldwell ◽  
S. DiNardo
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Tgf Beta ◽  
Signal Transducers ◽  
Daughter Cells ◽  
Stem Cell Lineage ◽  
Mosaic Analysis ◽  
Cyst Cells

To identify regulators of stem cell lineages, we are focusing on spermatogenesis in Drosophila. In spermatogenesis, each germline stem cell divides asymmetrically, renewing itself and producing a transiently amplifying daughter, which divides four times. By screening for mutants in which daughter cells fail to stop dividing, we find that the TGF-beta signal transducers schnurri and punt are required to limit transient amplification of germ cells. Mosaic analysis demonstrates that punt and schnurri act within somatic cyst cells that surround germ cells, rather than in germ cells. Thus, a cyst-cell-derived signal restricts germ cell proliferation and this signal is initiated by input from a member of the TGF-beta superfamily. Thus, a signal relay regulates progression through the germline stem cell lineage.

scholarly journals Adult stem cell lineage tracing and deep tissue imaging

BMB Reports ◽  
2015 ◽  
Vol 48 (12) ◽  
pp. 655-667 ◽  
Author(s):  
Juergen Fink ◽  
Amanda Andersson-Rolf ◽  
Bon-Kyoung Koo
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Tissue Imaging ◽  
Deep Tissue ◽  
Stem Cell Lineage ◽  
Deep Tissue Imaging

scholarly journals Accumulation of a differentiation regulator specifies transit amplifying division number in an adult stem cell lineage

2009 ◽  
Vol 106 (52) ◽  
pp. 22311-22316 ◽  
Author(s):  
Megan L. Insco ◽  
Arlene Leon ◽  
Cheuk Ho Tam ◽  
Dennis M. McKearin ◽  
Margaret T. Fuller
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Stem Cell Lineage ◽  
Division Number

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 conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexis S Bailey ◽  
Pedro J Batista ◽  
Rebecca S Gold ◽  
Y Grace Chen ◽  
Dirk G de Rooij ◽  
...  
Keyword(s):  
Cell Fate ◽  
Germ Cells ◽  
Meiotic Prophase ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Male Germ Cells ◽  
Translational Repressor ◽  
Multiple Transcripts ◽  
Stem Cell Lineage ◽  
Post Transcriptional Regulation

The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.

bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4361-4371 ◽  
Author(s):  
P. Gonczy ◽  
E. Matunis ◽  
S. DiNardo
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Daughter Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Cell Lineages ◽  
Male Germline ◽  
Stem Cell Lineage ◽  
Cell Neoplasm ◽  
Bag Of Marbles

Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.

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 Notch signaling is required for survival of the germline stem cell lineage in testes of Drosophila melanogaster

2019 ◽  
Author(s):  
Chun L. Ng ◽  
Qian Yue ◽  
Schulz Cordula
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Notch Signaling ◽  
Transition Zone ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Stem Cell Lineage ◽  
Cyst Cells ◽  
Germline Cells

AbstractIn all metazoan species, sperm is produced from germline stem cells. These self-renew and produce daughter cells that amplify and differentiate dependent on interactions with somatic support cells. In the male gonad of Drosophila melanogaster, the germline and somatic cyst cells co-differentiate as cysts, an arrangement in which the germline is completely enclosed by cytoplasmic extensions from the cyst cells. Notch is a developmentally relevant receptor in a pathway requiring immediate proximity with the signal sending cell. Here, we show that Notch is expressed in the cyst cells of wild-type testes. Notch becomes activated in the transition zone, an apical area of the testes in which the cyst cells express stage-specific transcription factors and the enclosed germline finalizes transit-amplifying divisions. Reducing the ligand Delta from the germline cells via RNA-Interference or reducing the receptor Notch from the cyst cells via CRISPR resulted in cell death concomitant with loss of germline cells from the transition zone. This shows that Notch signaling is essential for the survival of the germline stem cell lineage.

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