Sexual dimorphism of niche architecture and regulation of the Caenorhabditis elegans germline stem cell pool

Stem cell maintenance by niche signaling is a common theme across phylogeny. In the Caenorhabditis elegans gonad, the broad outlines of germline stem cell (GSC) regulation are the same for both sexes: GLP-1/Notch signaling from the mesenchymal distal tip cell niche maintains GSCs in the distal gonad of both sexes and does so via two key stem cell regulators, SYGL-1 and LST-1. Yet most recent analyses of niche signaling and GSC regulation have focused on XX hermaphrodites, an essentially female sex making sperm in larvae and oocytes in adults. Here we focus on GSC regulation in XO males. Sexual dimorphism of niche architecture, reported previously, suggested that the molecular responses to niche signaling or numbers of GSCs might also be sexually distinct. Remarkably, this is not the case. This work extends our understanding of the sexually dimorphic niche architecture, but also demonstrates that the dimorphic niches drive a similar molecular response and maintain a similar number of GSCs in their stem cell pools.

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A DTC Niche Plexus Surrounds the Germline Stem Cell Pool in Caenorhabditis elegans

PLoS ONE ◽

10.1371/journal.pone.0088372 ◽

2014 ◽

Vol 9 (2) ◽

pp. e88372 ◽

Cited By ~ 43

Author(s):

Dana T. Byrd ◽

Karla Knobel ◽

Katharyn Affeldt ◽

Sarah L. Crittenden ◽

Judith Kimble

Keyword(s):

Stem Cell ◽

Caenorhabditis Elegans ◽

Germline Stem Cell ◽

Cell Pool ◽

Stem Cell Pool

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Doublesex regulates fruitless expression to promote sexual dimorphism of the gonad stem cell niche

PLoS Genetics ◽

10.1371/journal.pgen.1009468 ◽

2021 ◽

Vol 17 (3) ◽

pp. e1009468

Author(s):

Hong Zhou ◽

Cale Whitworth ◽

Caitlin Pozmanter ◽

Megan C. Neville ◽

Mark Van Doren

Keyword(s):

Stem Cell ◽

Alternative Splicing ◽

Sexual Dimorphism ◽

Ectopic Expression ◽

Transcriptional Level ◽

Specific Expression ◽

Stem Cell Maintenance ◽

Large Numbers ◽

Cell Niche ◽

Male Specific

Doublesex (Dsx) and Fruitless (Fru) are the two downstream transcription factors that actuate Drosophila sex determination. While Dsx assists Fru to regulate sex-specific behavior, whether Fru collaborates with Dsx in regulating other aspects of sexual dimorphism remains unknown. One important aspect of sexual dimorphism is found in the gonad stem cell (GSC) niches, where male and female GSCs are regulated to create large numbers of sperm and eggs. Here we report that Fru is expressed male-specifically in the GSC niche and plays important roles in the development and maintenance of these cells. Unlike previously-studied aspects of sex-specific Fru expression, which are regulated by Transformer (Tra)-mediated alternative splicing, we show that male-specific expression of fru in the gonad is regulated downstream of dsx, and is independent of tra. fru genetically interacts with dsx to support maintenance of the niche throughout development. Ectopic expression of fru inhibited female niche formation and partially masculinized the ovary. fru is also required autonomously for cyst stem cell maintenance and cyst cell survival. Finally, we identified a conserved Dsx binding site upstream of fru promoter P4 that regulates fru expression in the niche, indicating that fru is likely a direct target for transcriptional regulation by Dsx. These findings demonstrate that fru acts outside the nervous system to influence sexual dimorphism and reveal a new mechanism for regulating sex-specific expression of fru that is regulated at the transcriptional level by Dsx, rather than by alternative splicing by Tra.

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Faculty Opinions recommendation of JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733604418.793550197 ◽

2018 ◽

Author(s):

Todd Nystul

Keyword(s):

Stem Cell ◽

Chronic Stress ◽

Germline Stem Cell ◽

Jnk Signaling ◽

Cell Pool ◽

Drosophila Testis ◽

Stem Cell Pool

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JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis

eLife ◽

10.7554/elife.36095 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 11

Author(s):

Salvador C Herrera ◽

Erika A Bach

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Chronic Stress ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

Jnk Signaling ◽

Cell Pool ◽

Drosophila Testis ◽

Bag Of Marbles ◽

Stem Cell Pool

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.

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Analysis of GPI-anchored proteins involved in germline stem cell proliferation in the Caenorhabditis elegans germline stem cell niche

The Journal of Biochemistry ◽

10.1093/jb/mvaa075 ◽

2020 ◽

Vol 168 (6) ◽

pp. 589-602

Author(s):

Marika Rikitake ◽

Ayako Matsuda ◽

Daisuke Murata ◽

Katsufumi Dejima ◽

Kazuko H Nomura ◽

...

Keyword(s):

Cell Proliferation ◽

Stem Cell ◽

Caenorhabditis Elegans ◽

Lipid Rafts ◽

Stem Cell Niche ◽

Germline Stem Cell ◽

Self Renewal ◽

Stem Cell Proliferation ◽

Cell Niche ◽

Germline Stem Cell Niche

Abstract Stem cells divide and undergo self-renewal depending on the signals received from the stem cell niche. This phenomenon is indispensable to maintain tissues and organs in individuals. However, not all the molecular factors and mechanisms of self-renewal are known. In our previous study, we reported that glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) synthesized in the distal tip cells (DTCs; the stem cell niche) are essential for germline stem cell proliferation in Caenorhabditis elegans. Here, we characterized the GPI-APs required for proliferation. We selected and verified the candidate GPI-APs synthesized in DTCs by RNA interference screening and found that F57F4.3 (GFI-1), F57F4.4 and F54E2.1 are necessary for germline proliferation. These proteins are likely involved in the same pathway for proliferation and activated by the transcription factor PQM-1. We further provided evidence suggesting that these GPI-APs act through fatty acid remodelling of the GPI anchor, which is essential for association with lipid rafts. These findings demonstrated that GPI-APs, particularly F57F4.3/4 and F54E2.1, synthesized in the germline stem cell niche are located in lipid rafts and involved in promoting germline stem cell proliferation in C. elegans. The findings may thus shed light on the mechanisms by which GPI-APs regulate stem cell self-renewal.

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Non-Smad-Dependent BMP signaling Determines the size of Germline Stem Cell Pool via the Soma

Mechanisms of Development ◽

10.1016/j.mod.2017.04.504 ◽

2017 ◽

Vol 145 ◽

pp. S174

Author(s):

Chen-Yuan Tseng ◽

Yu-Han Su ◽

Hwei-Jan Hsu

Keyword(s):

Stem Cell ◽

Bmp Signaling ◽

Germline Stem Cell ◽

Cell Pool ◽

Stem Cell Pool

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Aging germline stem cells in C. elegans

Innovation in Aging ◽

10.1093/geroni/igaa057.2644 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 740-740

Author(s):

E Jane Hubbard

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell System ◽

Cell Aging ◽

Germline Stem Cell ◽

Germline Stem Cells ◽

C Elegans ◽

Cell Pool ◽

Stem Cell System ◽

Stem Cell Pool

Abstract Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage. We use the C. elegans germline stem cell system as a model to study stem cell aging. This system combines a well-established model for aging with an accessible stem cell system, providing a unique opportunity to understand how aging influences stem cell dynamics. The germline stem/progenitor pool in in C. elegans becomes depleted over time. At the cellular level, aging influences both the size of the stem cell pool and the proliferation rate of stem cells. The flux of differentiated cells also affects how aging impacts the pool. This depletion is partially alleviated in mutants with reduced insulin/IGF-like signaling via inhibition of the transcription factor DAF-16/FOXO. In this role, DAF-16 does not act in the germ line, and its anatomical requirements are different from its previously described roles in larval germline proliferation, dauer control, and lifespan regulation. We found that DAF-16/FOXO is required in certain somatic cells in the proximal part of the reproductive system to regulate the stem cell pool. We also find that the degree to which various age-defying perturbations affect lifespan does not correlate with their effect on germline stem cell maintenance. We are investigating additional aspects of aging germline stem cells using this system.

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fruitless functions downstream of doublesex to promote sexual dimorphism of the gonad stem cell niche

10.1101/454546 ◽

2018 ◽

Cited By ~ 1

Author(s):

Hong Zhou ◽

Cale Whitworth ◽

Caitlin Pozmanter ◽

Megan C. Neville ◽

Mark Van Doren

Keyword(s):

Nervous System ◽

Stem Cell ◽

Alternative Splicing ◽

Sexual Dimorphism ◽

Ectopic Expression ◽

Transcriptional Level ◽

Specific Expression ◽

Stem Cell Maintenance ◽

Cell Niche ◽

Male Specific

SUMMARYBackgrounddoublesex (dsx) and fruitless (fru) are the two downstream transcription factors that actuate Drosophila sex determination. While dsx assists fru to regulate sex-specific behavior, whether fru collaborates with dsx in regulating other aspects of sexual dimorphism remains unknown. One important aspect of sexual dimorphism is found in the gonad stem cell (GSC) niches, where male and female GSCs are regulated to create large numbers of sperm and eggs.ResultsHere we report that Fru is expressed male-specifically in the GSC niche and plays important roles in the development and maintenance of these cells. Unlike previously studied regulation of sex-specific Fru expression, which is regulated by alternative splicing by Transformer (Tra), we show that male-specific expression of fru is regulated downstream of dsx, and is independent of Tra. Regulation of fru by dsx also occurs in the nervous system. fru genetically interacts with dsx to support maintenance of the hub throughout development. Ectopic expression of fru inhibited female niche formation and partially masculinized the ovary. fru is also required autonomously for cyst stem cell maintenance and cyst cell survival. Finally, we identified a conserved Dsx binding site upstream of fru promoter P4 that regulates fru expression in the hub, indicating that fru is likely a direct target for transcriptional regulation by Dsx.ConclusionsThese findings demonstrate that fru acts outside the nervous system to influence sexual dimorphism and reveal a new mechanism for regulating sex-specific expression of fru that is regulated at the transcriptional level by Dsx, rather than by alternative splicing by Tra.

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