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

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.

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

Development ◽

10.1242/dev.124.21.4361 ◽

1997 ◽

Vol 124 (21) ◽

pp. 4361-4371 ◽

Cited By ~ 4

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.

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

10.1101/682773 ◽

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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Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

PLoS Genetics ◽

10.1371/journal.pgen.1004797 ◽

2014 ◽

Vol 10 (11) ◽

pp. e1004797 ◽

Cited By ~ 20

Author(s):

Di Chen ◽

Chan Wu ◽

Shaowei Zhao ◽

Qing Geng ◽

Yu Gao ◽

...

Keyword(s):

Stem Cell ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Cell Lineage ◽

Germline Stem Cell ◽

Stem Cell Lineage

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Mechanisms of pluripotency and epigenetic reprogramming in primordial germ cells: lessons for the conversion of other cell types into the stem cell lineage

TURKISH JOURNAL OF BIOLOGY ◽

10.3906/biy-1407-16 ◽

2015 ◽

Vol 39 ◽

pp. 187-193 ◽

Cited By ~ 1

Author(s):

Suresh PALAMADAI KRISHNAN

Keyword(s):

Stem Cell ◽

Germ Cells ◽

Primordial Germ Cells ◽

Cell Lineage ◽

Cell Types ◽

Epigenetic Reprogramming ◽

Stem Cell Lineage

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

10.1101/2021.05.20.444930 ◽

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.

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