scholarly journals An autoregulatory switch in sex-specific phf7 transcription causes loss of sexual identity and tumors in the Drosophila female germline

Development ◽  
2020 ◽  
Vol 147 (17) ◽  
pp. dev192856
Author(s):  
Anne E. Smolko ◽  
Laura Shapiro-Kulnane ◽  
Helen K. Salz
Keyword(s):  
Germ Cell ◽  
Sexual Identity ◽  
Germ Cells ◽  
Transcriptional Repression ◽  
Feedback Mechanism ◽  
Phd Finger ◽  
Transcriptional Reprogramming ◽  
Male Germline ◽  
Regulatory Circuit ◽  
Female Germline

ABSTRACTMaintenance of germ cell sexual identity is essential for reproduction. Entry into the spermatogenesis or oogenesis pathway requires that the appropriate gene network is activated and the antagonist network is silenced. For example, in Drosophila female germ cells, forced expression of the testis-specific PHD finger protein 7 (PHF7) disrupts oogenesis, leading to either an agametic or germ cell tumor phenotype. Here, we show that PHF7-expressing ovarian germ cells inappropriately express hundreds of genes, many of which are male germline genes. We find that the majority of genes under PHF7 control in female germ cells are not under PHF7 control in male germ cells, suggesting that PHF7 is acting in a tissue-specific manner. Remarkably, transcriptional reprogramming includes a positive autoregulatory feedback mechanism in which ectopic PHF7 overcomes its own transcriptional repression through promoter switching. Furthermore, we find that tumorigenic capacity is dependent on the dosage of phf7. This study reveals that ectopic PHF7 in female germ cells leads to a loss of sexual identity and the promotion of a regulatory circuit that is beneficial for tumor initiation and progression.

scholarly journals An autoregulatory switch in sex-specific phf7 transcription causes loss of sexual identity and tumors in the Drosophila female germline

2020 ◽  
Author(s):  
Anne E. Smolko ◽  
Laura Shapiro-Kulnane ◽  
Helen K. Salz
Keyword(s):  
Germ Cell ◽  
Sexual Identity ◽  
Germ Cells ◽  
Transcriptional Repression ◽  
Feedback Mechanism ◽  
Phd Finger ◽  
Transcriptional Reprogramming ◽  
Male Germline ◽  
Regulatory Circuit ◽  
Female Germline

ABSTRACTMaintenance of germ cell sexual identity is essential for reproduction. Entry into the spermatogenesis or oogenesis pathway requires that the appropriate gene network is activated and the antagonist network is silenced. For example, in Drosophila female germ cells, forced expression of the testis-specific PHD finger protein 7 (PHF7) disrupts oogenesis leading to either an agametic or germ cell tumor phenotype. Here we show that PHF7 expressing ovarian germ cells inappropriately express hundreds of genes, many of which are male germline genes. We find that the majority of genes under PHF7 control in female germ cells are not under PHF7 control in male germ cells, suggesting that PHF7 is acting in a tissue-specific manner. Remarkably, transcriptional reprogramming includes a positive autoregulatory feedback mechanism in which ectopic PHF7 overcomes its own transcriptional repression through promoter switching. Furthermore, we find that tumorigenic capacity is dependent on the dosage of phf7. This study reveals that high levels of ectopic PHF7 in female germ cells leads to a loss of sexual identity and promotion of a regulatory circuit beneficial for tumor initiation and progression.

scholarly journals Germline masculinization by Phf7 in D. melanogaster requires its evolutionarily novel C-terminus and the HP1-family protein HP1D3csd

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Yuan Yang
Keyword(s):  
Sex Determination ◽  
Germ Cells ◽  
Transcriptome Profiling ◽  
Phd Finger ◽  
Intrinsic Factors ◽  
Male Germline ◽  
C Terminus ◽  
Family Protein ◽  
Key Factor ◽  
Female Germline

AbstractGerm cells inDrosophila melanogasterneed intrinsic factors along with somatic signals to activate proper sexual programs. A key factor for male germline sex determination is PHD finger protein 7 (Phf7), a histone reader expressed in the male germline that can trigger sex reversal in female germ cells and is also important for efficient spermatogenesis. Here we find that the evolutionarily novel C-terminus in Phf7 is necessary to turn on the complete male program in the early germline ofD. melanogaster, suggesting that this domain may have been uniquely acquired to regulate sexual differentiation. We further looked for genes regulated byPhf7related to sex determination in the embryonic germline by transcriptome profiling of FACS-purified embryonic gonads. One of the genes positively-regulated by Phf7 in the embryonic germline was anHP1family member,Heterochromatin Protein 1D3 chromoshadow domain (HP1D3csd).We find that this gene is needed for Phf7 to induce male-like development in the female germline, indicating that HP1D3csd is an important factor acting downstream of Phf7 to regulate germline masculinization.

scholarly journals tudor-domain containing protein 5-prime promotes male sexual identity in the Drosophila germline and is repressed in females by Sex lethal

2018 ◽  
Author(s):  
Shekerah Primus ◽  
Caitlin Pozmanter ◽  
Kelly Baxter ◽  
Mark Van Doren
Keyword(s):  
Germ Cell ◽  
Sexual Identity ◽  
Germ Cells ◽  
Expression Profiling ◽  
Female Identity ◽  
Rna Expression ◽  
Male Identity ◽  
Male Germline ◽  
Tudor Domain ◽  
Rna Expression Profiling

AbstractFor sexually reproducing organisms, production of male or female gametes depends on specifying the correct sexual identity in the germline. In D. melanogaster, Sex lethal (Sxl) is the key gene that controls sex determination in both the soma and the germline, but how it does so in the germline is unknown, other than that it is different than in the soma. We conducted an RNA expression profiling experiment to identify direct and indirect germline targets of Sxl specifically in the undifferentiated germline. We find that, in these cells, Sxl loss does not lead to a global masculinization observed at the whole-genome level. In contrast, Sxl appears to affect a discrete set of genes required in the male germline, such as Phf7. We also identify tudor domain containing protein 5-prime (tdrd5p) as a target for Sxl regulation that is important for male germline identity. tdrd5p is repressed by Sxl in female germ cells, but is highly expressed in male germ cells where it promotes proper male fertility and germline differentiation. Additionally, Tdrd5p localizes to cytoplasmic granules with some characteristics of RNA Processing (P-) Bodies, suggesting that it promotes male identity in the germline by regulating post-transcriptional gene expression.Author summaryLike humans, all sexually reproducing organisms require gametes to reproduce. Gametes are made by specialized cells called germ cells, which must have the correct sexual identity information to properly make sperm or eggs. In fruit flies, germ cell sexual identity is controlled by the RNA-binding protein Sxl, which is expressed only in females. To better understand how Sxl promotes female identity, we conducted an RNA expression profiling experiment to identify genes whose expression changes in response to the loss of Sxl from germ cells. Here, we identify tudor domain containing protein 5-prime (tdrd5p), which is expressed 17-fold higher in ovaries lacking Sxl compared to control ovaries. Additionally, tdrd5p plays an important role in males as male flies that are mutant for this gene cannot make sperm properly and thus are less fertile. Moreover, we find that tdrd5p promotes male identity in the germline, as several experiments show that it can shift the germ cell developmental program from female to male. This study tells us that Sxl promotes female identity in germ cells by repressing genes, like tdrd5p, that promote male identity. Future studies into the function of tdrd5p will provide mechanistic insight into how this gene promotes male identity.

scholarly journals The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Zezheng Pan ◽  
Mengli Sun ◽  
Xia Liang ◽  
Jia Li ◽  
Fangyue Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Mammalian Species ◽  
Research Progress ◽  
Germline Stem Cells ◽  
Conventional View ◽  
Proliferation And Differentiation ◽  
Potential Benefits ◽  
Female Germline

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.

The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 561-577 ◽  
Author(s):  
R E Ellis ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Sexual Identity ◽  
Cell Fate ◽  
Germ Cells ◽  
Regulatory Network ◽  
Germ Line ◽  
The Other ◽  
Nematode Caenorhabditis Elegans ◽  
Inhibitory Interactions

Abstract In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two.

scholarly journals Germline Sex Determination regulates sex-specific signaling between germline stem cells and their niche

2021 ◽  
Author(s):  
Pradeep Kumar Bhaskar ◽  
Sheryl Southard ◽  
Kelly Baxter ◽  
Mark Van Doren
Keyword(s):  
Stem Cells ◽  
Sex Determination ◽  
Sexual Identity ◽  
Germ Cells ◽  
Sex Chromosome ◽  
Germline Stem Cells ◽  
Somatic Gonad ◽  
Stat Signaling ◽  
Female Germline ◽  
Germline Sex Determination

SummaryThe establishment of sexual identity in germ cells is critical for the development of male and female germline stem cells (GSCs) and production of sperm vs. eggs. Thus, this process is essential for sexual reproduction and human fertility. Germ cells depend on signals from the somatic gonad to determine their sex, but in organisms such as flies, mice and humans, the sex chromosome genotype of the germ cells is also important for germline sexual development. How somatic signals and germ cell-intrinsic cues act together to regulate germline sex determination is a key question about which little is known. We have found that JAK/STAT signaling in the GSC niche promotes male identity in germ cells and GSCs, in part by activating expression of the epigenetic reader Phf7. We have also found that JAK/STAT signaling is blocked in XX (female) germ cells through the intrinsic action of the sex determination gene Sex lethal, which preserves female identity. Thus, an important function of germline sexual identity is to control how GSCs respond to signals in their niche environment.

Sex Determination Signals Control ovo-B Transcription in Drosophila melanogaster Germ Cells

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 537-545
Author(s):  
Justen Andrews ◽  
Brian Oliver
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Genetic Analysis ◽  
Sex Determination ◽  
Sexual Identity ◽  
Germ Cells ◽  
Female Germline ◽  
Chromosome Karyotype ◽  
Inductive Signals

Abstract Nonautonomous inductive signals from the soma and autonomous signals due to a 2X karyotype determine the sex of Drosophila melanogaster germ cells. These two signals have partially overlapping influences on downstream sex determination genes. The upstream OVO-B transcription factor is required for the viability of 2X germ cells, regardless of sexual identity, and for female germline sexual identity. The influence of inductive and autonomous signals on ovo expression has been controversial. We show that ovo-B is strongly expressed in the 2X germ cells in either a male or a female soma. This indicates that a 2X karyotype controls ovo-B expression in the absence of inductive signals from the female soma. However, we also show that female inductive signals positively regulate ovo-B transcription in the 1X germ cells that do not require ovo-B function. Genetic analysis clearly indicates that inductive signals from the soma are not required for ovo-B function in 2X germ cells. Thus, while somatic inductive signals and chromosome karyotype have overlapping regulatory influences, a 2X karyotype is a critical germline autonomous determinant of ovo-B function in the germline.

scholarly journals RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility

2020 ◽  
Author(s):  
Peiwei Chen ◽  
Yicheng Luo ◽  
Alexei A. Aravin
Keyword(s):  
Germ Cells ◽  
Male Fertility ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Pirna Cluster ◽  
Transposon Silencing ◽  
Normal Spermatogenesis ◽  
Non Coding Rnas ◽  
Female Germline ◽  
Active Genes

SUMMARYpiRNAs are small non-coding RNAs that guide the silencing of transposons and other targets in animal gonads. In Drosophila female germline, many piRNA source loci dubbed ‘piRNA clusters’ lack hallmarks of active genes and exploit an alternative path for transcription, which relies on the Rhino-Deadlock-Cutoff (RDC) complex. It remains to date unknown how piRNA cluster transcription is regulated in the male germline. We found that components of RDC complex are expressed in male germ cells during early spermatogenesis, from germline stem cells (GSCs) to early spermatocytes. RDC is essential for expression of dual-strand piRNA clusters and transposon silencing in testis; however, it is dispensable for expression of Y-linked Suppressor of Stellate piRNAs and therefore Stellate silencing. Despite intact Stellate repression, rhi mutant males exhibited compromised fertility accompanied by germline DNA damage and GSC loss. Thus, piRNA-guided repression is essential for normal spermatogenesis beyond Stellate silencing. While RDC associates with multiple piRNA clusters in GSCs and early spermatogonia, its localization changes in later stages as RDC concentrates on a single X-linked locus, AT-chX. Dynamic RDC localization is paralleled by changes in piRNA cluster expression, indicating that RDC executes a fluid piRNA program during different stages of spermatogenesis.

scholarly journals Specification of germ cell fate in mice

2003 ◽  
Vol 358 (1436) ◽  
pp. 1363-1370 ◽  
Author(s):  
Mitinori Saitou ◽  
Bernhard Payer ◽  
Ulrike C. Lange ◽  
Sylvia Erhardt ◽  
Sheila C. Barton ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Transcriptional Repression ◽  
Single Cell Analysis ◽  
Primordial Germ Cells ◽  
Cell Specification ◽  
Signalling Molecules ◽  
Germ Cell Specification

An early fundamental event during development is the segregation of germ cells from somatic cells. In many organisms, this is accomplished by the inheritance of preformed germ plasm, which apparently imposes transcriptional repression to prevent somatic cell fate. However, in mammals, pluripotent epiblast cells acquire germ cell fate in response to signalling molecules. We have used single cell analysis to study how epiblast cells acquire germ cell competence and undergo specification. Germ cell competent cells express Fragilis and initially progress towards a somatic mesodermal fate. However, a subset of these cells, the future primordial germ cells (PGCs), then shows rapid upregulation of Fragilis with concomitant transcriptional repression of a number of genes, including Hox and Smad genes. This repression may be a key event associated with germ cell specification. Furthermore, PGCs express Stella and other genes, such as Oct – 4 that are associated with pluripotency. While these molecules are also detected in mature oocytes as maternally inherited factors, their early role is to regulate development and maintain pluripotency, and they do not serve the role of classical germline determinants.

scholarly journals Male germline development in the tammar wallaby, Macropus eugenii

Reproduction ◽  
2021 ◽  
Vol 161 (3) ◽  
pp. 333-341
Author(s):  
Teruhito Ishihara ◽  
Oliver W Griffith ◽  
Gerard A Tarulli ◽  
Marilyn B Renfree
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Evolutionary History ◽  
Tammar Wallaby ◽  
Mitotic Arrest ◽  
Germline Development ◽  
Macropus Eugenii ◽  
Male Germline ◽  
Cell Mitosis

Male germ cells undergo two consecutive processes – pre-spermatogenesis and spermatogenesis – to generate mature sperm. In eutherian mammals, epigenetic information such as DNA methylation is dynamically reprogrammed during pre-spermatogenesis, before and during mitotic arrest. In mice, by the time germ cells resume mitosis, the majority of DNA methylation is reprogrammed. The tammar wallaby has a similar pattern of germ cell global DNA methylation reprogramming to that of the mouse during early pre-spermatogenesis. However, early male germline development in the tammar or in any marsupial has not been described previously, so it is unknown whether this is a general feature regulating male germline development or a more recent phenomenon in mammalian evolutionary history. To answer this, we examined germ cell nuclear morphology and mitotic arrest during male germline development in the tammar wallaby (Macropus eugenii), a marsupial that diverged from mice and humans around 160 million years ago. Tammar pro-spermatogonia proliferated after birth and entered mitotic arrest after day 30 postpartum (pp). At this time, they began moving towards the periphery of the testis cords and their nuclear size increased. Germ cells increased in number after day 100 pp which is the time that DNA methylation is known to be re-established in the tammar. This is similar to the pattern observed in the mouse, suggesting that resumption of germ cell mitosis and the timing of DNA methylation reprogramming are correlated and conserved across mammals and over long evolutionary timescales.

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