InteractiveFly: GeneBrief

Pelota: Biological Overview | Regulation | Developmental Biology | Effects of Mutation | Evolutionary Homologs | References

Gene name - pelota

Synonyms -

Cytological map position - 30C5

Function - translation factor

Keywords - meiosis, oogenesis, spermatogenesis, eye

Symbol - pelo

FlyBase ID: FBgn0011207

Genetic map position - 2L

Classification - eRF1 domain protein

Cellular location - cytoplasmic

NCBI links: Precomputed BLAST | EntrezGene
Recent literature
Yang, F., Zhao, R., Fang, X., Huang, H., Xuan, Y., Ma, Y., Chen, H., Cai, T., Qi, Y. and Xi, R. (2015). The RNA surveillance complex Pelo-Hbs1 is required for transposon silencing in the Drosophila germline. EMBO Rep [Epub ahead of print]. PubMed ID: 26124316
Silencing of transposable elements (TEs) in the metazoan germline is critical for genome integrity and is primarily dependent on Piwi proteins and associated RNAs, which exert their function through both transcriptional and posttranscriptional mechanisms. This study reports that the evolutionarily conserved Pelo (Dom34)-Hbs1 mRNA surveillance complex is required for transposon silencing in the Drosophila germline. In pelo mutant gonads, mRNAs and proteins of some selective TEs are up-regulated. Pelo is not required for piRNA biogenesis, and Pelo may function at the translational level to silence TEs: this function requires interaction with Hbs1, and overexpression of RpS30a partially reverts TE-silencing defects in pelo mutants. Interestingly, TE silencing and spermatogenesis defects in pelo mutants can also effectively be rescued by expressing the mammalian ortholog of Pelo. The study proposes that the Pelo-Hbs1 surveillance complex provides another level of defense against the expression of TEs in the germline of Drosophila and possibly all metazoa.
Hashimoto, Y., Takahashi, M., Sakota, E. and Nakamura, Y. (2017). Nonstop-mRNA decay machinery is involved in the clearance of mRNA 5'-fragments produced by RNAi and NMD in Drosophila melanogaster cells. Biochem Biophys Res Commun 484(1): 1-7. PubMed ID: 28115162
When translating mRNAs are cleaved in protein-coding regions, 5' fragments of mRNAs are detached from stop codons (i.e., nonstop mRNAs) and protected from 3'-5' exonucleases by ribosomes stalled at the 3' termini. It has been shown in yeast that the nonstop mRNA decay (NSD) machinery triggers nonstop mRNA degradation by removing stalled ribosomes in the artificial reporter mRNAs. However, it is not known well whether NSD is involved in the degradation of endogenous nonstop mRNAs in higher eukaryotes. The question of whether 5'-nonstop-mRNA fragments generated by siRNA cleavage or nonsense-mediated-mRNA decay (NMD) are degraded by the NSD pathway in was addressed Drosophila melanogaster cells by knocking down three NSD components, Pelota (a yeast Dom34 homolog), Hbs1 and ABCE1 (a ribosome-recycling factor). Double, but not single, knockdown of any two of these three factors efficiently stabilized nonstop reporter mRNAs and triple knockdown of Pelota, Hbs1 and ABCE1 further stabilized nonstop mRNAs in highly ribosome-associated state. These findings demonstrated that Pelota, Hbs1 and ABCE1 are crucial for NSD in Drosophila cells as in yeast for rescuing stalled ribosomes and degrading nonstop mRNAs. This is the first comprehensive report to show the involvement of the NSD machinery in the clearance of mRNA 5'-fragments produced by RNAi and NMD in eukaryotes.

In the Drosophila ovary, germline stem cell (GSC) self-renewal is controlled by both extrinsic and intrinsic factors. The Bmp signal from niche cells controls GSC self-renewal by directly repressing a Bam-dependent differentiation pathway in GSCs. pelota (pelo), which has been previously shown to be required for Drosophila male meiosis, was identified in a genetic screen as a dominant suppressor of the dpp overexpression-induced GSC tumor phenotype. Pelo acts in controlling GSC self-renewal by repressing a Bam-independent differentiation pathway. In pelo mutant ovaries, GSCs are lost rapidly owing to differentiation. Results from genetic mosaic analysis and germ cell-specific rescue show that it functions as an intrinsic factor to control GSC self-renewal. In pelo mutant GSCs, Bmp signaling activity detected by Dad-lacZ expression is downregulated, but bam expression is still repressed. Furthermore, bam mutant germ cells are still able to differentiate into cystocytes without pelo function, indicating that Pelo is involved in repressing a Bam-independent differentiation pathway. Consistent with its homology to the eukaryotic translation release factor 1alpha, Pelo is shown to be localized to the cytoplasm of the GSC. Therefore, Pelo controls GSC self-renewal by repressing a Bam-independent differentiation pathway possibly through regulating translation. Since Pelo is highly conserved from Drosophila to mammals, it may also be involved in the regulation of adult stem cell self-renewal in mammals, including humans (Xi, 2005).

Stem cells are characterized by their ability to self-renew and generate differentiated cells throughout the lifetime of an organism. Understanding how stem cell self-renewal is controlled is an important issue in stem cell biology and will help realize the potentials inherent in stem cell-based therapies. Studies from diverse systems indicate that stem cell self-renewal is controlled by both extrinsic factors (niche signals) and intrinsic factors. Niche signals have been shown to control GSC self-renewal by directly repressing expression of differentiation-promoting genes in the Drosophila ovary (Chen, 2003a; Song, 2004). Therefore, the identification of pathways and genes that repress stem cell differentiation is crucial for understanding how stem cell self-renewal is controlled (Xi, 2005).

In the Drosophila ovary, GSCs reside in a structure called the germarium, which is at the anterior end of an ovariole (Lin, 2002; Xie, 2001). At the anterior tip of the germarium, three types of somatic cells (terminal filament cells, cap cells and inner sheath cells) constitute a niche that supports two or three GSCs (Lin, 2002; Xie, 2001; Xie, 2000). One GSC divides to generate two daughter cells: the daughter cell maintaining contact with the cap cells through DE-cadherin-mediated cell adhesion renews itself as a stem cell, while the daughter cell moving away from the cap cells differentiates into a cystoblast (Song, 2002b). The cystoblast divides four times with incomplete cytokinesis to form a 16-cell cyst in which one cell becomes an oocyte and the rest become nurse cells. The Bmp signals that are produced by the niche, Dpp and Gbb, have essential roles in controlling GSC self-renewal: reduction of Bmp signaling activity results in the loss of GSCs by differentiation; overexpression of dpp in the germarium produces GSC-like tumors (Song, 2004; Xie, 1998). Bmps from the cap cells function as short-range signals that directly repress the transcription of bam in GSCs to maintain their self-renewal, and also allow cystoblasts lying one cell diameter away to differentiate (Chen, 2003a; Song, 2004). bam is necessary and sufficient for germ cell differentiating in the Drosophila ovary. In addition, two other genes, Yb and piwi, function in the somatic niche cells to control GSC (Cox, 2000; King, 2001). Yb encodes a novel protein and directly regulates expression of piwi and hh in TFs; hh signaling also modulates GSC self-renewal though it is not essential (King, 2001). piwi encodes a family of conserved RNA-binding proteins and is required in the niche cells for controlling GSC self-renewal and inside GSCs for their division. Two recent studies have shown that piwi also maintains GSC self-renewal by repressing bam expression through regulation of either the Bmp signaling pathway or a Bmp-independent signaling pathway (Chen, 2005; Szakmary, 2005). However, it remains unclear how piwi controls GSC division intrinsically (Xi, 2005).

Two translational repressors, Nanos (Nos) and Pumilio (Pum), have been shown to be required for the maintenance of ovarian GSCs by preventing differentiation. Pum/Nos repress differentiation of PGCs and GSCs through a Bmp-independent pathway; their expression is not regulated by Bmp signaling and their mutations cannot suppress hyperactive Bmp signaling-induced PGC proliferation. It is likely that Nos and Pum are involved in repressing translation gene products that are important for germ cell differentiation and thereby for controlling GSC self-renewal. To identify further intrinsic factors that are required for Bmp-mediated GSC self-renewal, a genetic screen was performed to identify dominant suppressors of the dpp-induced GSC-like tumor phenotype. One of the suppressors is pelota (pelo), which has been studied for its role in the regulation of Drosophila male meiosis. Cellular and molecular analysis showed that pelo is required for the progression through meiosis in spermatogenesis and encodes an evolutionarily conserved protein that contains a eukaryotic release factor 1 alpha (eRF1alpha)-like domain at its C terminus (Eberhart, 1995). The studies on the yeast pelo homolog dom34 suggest that Pelo is involved in translational regulation. Deletion of Dom34 causes growth retardation, defective sporulation and reduces polyribosomes (Davis, 1998). dom34 has a strong genetic interaction with RPS30A, which encodes ribosomal protein S30A; overexpression of RPS30A rescues the growth defects and reduced polyribosomes of dom34 mutants (Davis, 1998). Moreover, Dom34 specifically interacts with Hbs1, a small GTPase that is also implicated in translational regulation (Carr-Schmid, 2002). It has been recently shown that pelo knockout mice exhibit early embryonic lethality with defects in cell division and proliferation (Adham, 2003). Taken together, pelo may be involved in the regulation of meiosis and mitosis possibly through regulating translation. In this study, an unexpected new role has been discovered for Pelo in the control of GSC self-renewal and division in the Drosophila ovary, possibly through regulating translation (Xi, 2005).

It has been shown that bam is both essential and sufficient for cystoblast differentiation. The observation that pelo1 mutant GSCs are lost because of differentiation but do not upregulate bam expression suggests that pelo mutant GSCs differentiate using a bam-independent pathway. If so, it should be expected that bam mutant germ cells would be able to differentiate in the absence of pelo function. To test this idea, the genetic relationship between bam and pelo was investigated. The pelo1 homozygous GSCs that were heterozygous for bamDelta86, a deletion allele of bam, were still lost rapidly as in the pelo1 mutant GSCs; the bamDelta86 homozygous germ cells that were also heterozygous for pelo1 still failed to differentiate, as did the bamDelta86 mutant one. Interestingly, in pelo1; bamDelta86 double homozygous germaria, most of the germ cells were cysts with branched fusomes, and some of them still retained a round spectrosome. Unusually, the round spectrosomes in the remaining single germ cells were larger than those in bam mutant single germ cells, suggesting the single germ cells could be growth-arrested cystoblasts but can continue to grow their spectrosome. The morphology of the branched fusomes of the double mutant cysts appeared abnormal. To further determine whether the oocytes form in these pelo; bam mutant cysts, the expression of Orb protein was examined in the double mutant germaria. Orb normally starts to accumulate in newly formed wild-type oocytes; however, no obvious Orb expression was detected in the pelo; bam mutant germaria, indicating that there is no oocyte formation in the double mutant cysts. Since pelo mutant cysts can still form the oocyte, bam is probably required late for oocyte formation. These findings show that pelo mutant cystoblasts can differentiate without functional bam, and further suggest that pelo must repress a bam-independent differentiation pathway to maintain GSC self-renewal (Xi, 2005).

This study has revealed a new function of pelo in controlling GSC self-renewal in the Drosophila ovary. Genetic clonal analysis and rescue experiment results show that Pelo is required intrinsically for controlling GSC self-renewal. It is involved in the regulation of some Bmp response in GSCs but is not required for repressing bam expression. Genetic analysis further indicates that it controls GSC self-renewal by repressing a bam-independent differentiation pathway. Although translational control has been implicated in the regulation of GSC self-renewal, this is the first time it has been shown that a translational release factor-like protein controls GSC self-renewal. Since Pelo is highly conserved from Drosophila to human, it is also possible that its mammalian homologs might also be involved in the control of stem cell self-renewal (Xi, 2005).

Drosophila Pelo belongs to a family of evolutionarily conserved proteins with their primary function in the regulation of cell division. In the yeast, dom34 (pelo) mutant cells grow slowly and have defects in the entry of meiosis, indicating that it is required for mitosis and meiosis. In mice, disruption of the pelo gene causes early embryonic lethality and defects in cell cycle progression (Adham, 2003). Although pelo is ubiquitously expressed throughout Drosophila development (Eberhart, 1995), the pelo mutants survive to adulthood without obvious defects in the body. In Drosophila, pelo has been shown to be required to control meiotic cell cycle progression in male germ cells. In this study, pelo has been shown to be required intrinsically for controlling self-renewal and division of GSCs but not SSCs in the ovary; this requirement is supported by rescue and stem cell clonal analysis experiments. Even though Pelo members are required for regulating cell cycle progression from yeast to mammals, it remains unclear how they accomplish this function (Xi, 2005).

The only clue to the potential cellular function of Pelo comes from its high homology to the translation release factor 1. Its likely function as a translational regulator is further complicated by the presence of a highly conserved NLS sequence (Eberhart, 1995). Using an epitope-tagged Pelo that can rescue pelo mutants, it was demonstrated that Pelo is mainly localized to the cytoplasm of both S2 cells and germ cells. Furthermore, the pelo gene with a mutated putative NLS is still fully functional. The yeast Pelo, Dom34, is also localized to the cytoplasm (Davis, 1998; Huh, 2003). These findings support the idea that Pelo proteins function in the cytoplasm as translational regulators in different organisms. If Pelo protein truly functions as a translational release factors,it must directly interact with ribosomes that are either associated with ER or in the cytoplasm. Consistent with this idea, some Pelo proteins are associated with ER membranes though the majority of Pelo proteins are not associated with ER membranes. In yeast, dom34 mutants have dramatically reduced polyribosomes and can be rescued by a high-copy of the ribosomal protein S30A gene, indicating that Dom34 is involved in translation (Davis, 1998). In addition, expression of Drosophila pelo in dom34 mutants can rescue growth defects, indicating its conserved function during evolution. Therefore, Pelo is also likely a translational regulator in Drosophila, and is involved in regulating translation of a specific class of mRNAs that are important for germ cell function. In the future, it will be important to investigate whether Pelo is indeed involved in translational regulation and to identify its targets in germ cells (Xi, 2005).

Before this work, pelo had not been shown to be involved in regulating any signaling pathways in any organisms. The Bmp pathway is a major signaling pathway that is essential for controlling GSC self-renewal and division in the Drosophila ovary (Song, 2004; Xie, 1998). The Bmp signaling activities can be reliably monitored by expression of Dad in GSCs. It is anticipated that pelo must somehow interact with the Bmp pathway in controlling GSC self-renewal, since pelo was also identified as a dominant suppressor of Dpp overexpression-induced GSC-like tumors. In this study, GSCs mutant for pelo are shown to downregulate Dad. These findings indicate that Pelo participates in Bmp signaling to control expression of dpp target genes in GSCs such as Dad (Xi, 2005).

In the Drosophila ovary, one of the ways in which Bmp signaling controls GSC self-renewal is to directly repress bam expression in GSCs. bam is necessary and sufficient for cystoblast differentiation in the Drosophila ovary. In this study, Pelo is shown to be essential for controlling GSC self-renewal but is not involved in repressing bam expression. pelo mutant GSCs have normal bam repression but their progeny can still differentiate without bam, suggesting that pelo maintains GSCs by repressing a bam-independent pathway. During the preparation of this manuscript, two studies were published showing that pum controls GSC self-renewal by repressing a bam-independent pathway (Chen, 2005; Szakmary, 2005). Pum is known to work together with Nos, which is also essential for Drosophila ovarian GSC self-renewal, to repress gene translation in the embryo. Since Pum/Nos does not participate in Bmp signaling and Pelo is a translational release factor-like protein, it is proposed that Pelo works in a parallel genetic pathway with Pum in repressing the same or different Bam-independent differentiation pathways through regulating translation. Although it is essential for repressing a Bam-independent pathway(s) in GSCs, Pelo is not so sufficient for doing so; Bmp signaling functions to repress bam, as evidenced by the observation that overexpression of pelo has no effect on the GSC maintenance and differentiation. In the future, it will be important to molecularly and genetically characterize the Bam-independent pathway repressed by Pelo and to further understand how Pelo represses it in relation to Pum (Xi, 2005).


Targets of Activity: pelo modulates dpp signaling

pelo was identified in a genetic screen looking for genes that can suppress dpp overexpression-induced GSC-like tumors, suggesting that pelo must somehow genetically interact with the dpp/Bmp pathway. To further reveal the relationship between pelo and Bmp signaling, the dose effect of pelo on dpp-induced GSC-like tumor formation was carefully examined. As reported previously (Xie, 1998; Song, 2004), ovarioles overexpressing dpp by the c587 gal4 driver contain only single germ cells resembling GSCs. Among the dpp-overexpressing ovarioles also carrying one copy of the pelo1 mutation, 36% of them showed the same tumor phenotype, but the rest of the ovarioles contained differentiated germline cysts, developing egg chambers and even mature eggs, which could explain why pelo was identified in the suppressor screen. Among the dpp-overexpressing ovarioles also carrying two copies of the pelo1 mutations, only 13.8% of them contained only GSC-like single germ cells, while 49.8% of them had a mixture of single germ cells and developing cysts. Interestingly, the rest (36.4%) were reminiscent of the pelo GSC loss phenotype only. These results suggest that pelo functions as one of the Bmp downstream components or in a pathway parallel to the Bmp signaling pathway to control GSC self-renewal (Xi, 2005).

To further understand how pelo modulates Bmp signaling activity, the expression of a Bmp direct target gene, Dad, was examined in the pelo mutant GSCs. Dad-lacZ is a lacZ enhancer trap line for Dad. Its expression is the strongest in the GSCs, and is quickly downregulated in the differentiating cystoblasts. The pelo1 mutant GSCs marked by loss of ubi-GFP expression were generated by the FLP-mediated FRT recombination, and then were analyzed for Dad-lacZ expression 2 weeks after clone induction. Consistent with the idea that pelo is involved in modulating Bmp signaling, 69% of the marked mutant pelo GSCs (GFP negative) showed the downregulation of Dad-lacZ expression in comparison with their neighboring wild-type GSCs (GFP-positive). It was further asked whether pelo is also involved in Bmp-mediated bam repression in GSCs, since Bmp signaling has been shown to directly represses bam transcription in GSCs. A bam-GFP transgene (a GFP reporter driven by a bam promoter) is repressed in GSCs, while its expression is upregulated in the differentiating cystoblasts (Chen, 2003b). The marked pelo mutant GSCs (lacZ negative) were generated by the FLP-mediated FRT recombination and were examined for bam expression. Only about 5% of the marked pelo mutant GSCs (lacZ negative) showed slight upregulation of bam-GFP in comparison with their neighboring unmarked wild-type GSCs (lacZ positive), while the rest of the marked pelo1 mutant GSCs did not upregulate bam-GFP expression. These findings indicate that Pelo is involved in modulating Bmp signaling in GSCs but plays little or no role in regulating Bmp-mediated bam repression, and further suggest that it functions in one branch of the responses of the Bmp signaling pathway to regulate GSC self-renewal (Xi, 2005).


The pelota transcript is present in all developmental stages examined, but is most abundant in 0-2 hour old embryos and adults. The larval transcript appeared larger in some, but not all, northern blot experiments. The 2.1 kb transcript is present in the germlineless progeny of oskar mutant flies and in iab4 flies that lack a gonad. Thus the pelota transcript is not restricted to the germline or gonad. In pelo mutant adults both genomic and cDNA probes detected only a 1.1 kb transcript, presumably a truncation of the 2.1 kb transcript due to insertion of the transposon (Eberhart, 1995).


The pelota locus encodes a protein required for meiotic cell division: an analysis of G2/M arrest in Drosophila spermatogenesis

During Drosophila spermatogenesis, germ cells undergo four rounds of mitosis, an extended premeiotic G2 phase and two meiotic divisions. In males homozygous for mutations in pelota, the germline mitotic divisions are normal, but the cell cycle arrests prior to the first meiotic division; pelota males are therefore sterile. Chromosomes begin to condense in these mutants, but other meiotic processes, including nuclear envelope breakdown and spindle formation, do not occur. The arrest phenotype closely resembles that of mutations in the Drosophila cdc25 homolog Twine. Although meiosis is blocked in pelota and twine homozygotes, spermatid differentiation continues. pelota is also required for patterning in the eye and mitotic divisions in the ovary. The pelota locus has been cloned and shown to encodes a 44x103 Mr protein with yeast, plant, worm and human homologs (Eberhart, 1995).

In males homozygous for pelo1, the cell cycle in spermatocytes arrests either just before or very early in the first meiotic cell division. The apical regions of a testis from a pelo1 homozygote appear normal, filled with visibly wild-type mitotic and growth phase cysts. The rest of the testis, which usually contains 64-cell spermatid cysts, is instead filled with 16-cell cysts. The spermatocytes attain their mature size. Furthermore, they undergo a premeiotic S phase, as evidenced by the incorporation of bromodeoxyuridine into 16-cell cysts in pelota testes. However, meiotic figures, which can be easily recognized in squashed preparations of wild-type testes, are never seen (Eberhart, 1995).

While meiotic divisions do not occur in pelo1 spermatocytes, other aspects of spermatogenesis continue, resulting in 4N spermatids. In wild-type testes, the round, dark nebenkern is the first major cytoplasmic structure to form after meiosis. It is made up of mitochondria and serves as a marker for postmeiotic cytoplasmic development. Germline cells in pelo1 testes develop into 4N spermatids containing nebenkerne. As nebenkerne form, the pelo1 nuclei shrink in size by one third to spermatid head and tail structures. The content of testes from flies trans-heterozygous for pelo1 and Df(2L)30A;C, a deficiency for the pelota region, are indistinguishable from those of pelo1 homozygotes. Thus, pelo1 is a strong allele and possibly a null (Eberhart, 1995).

The pelo1 testis phenotype -- limited spermatid development in the absence of meiosis -- closely resembles that of a mutation in the cell cycle gene twine. Although the proportion of 4N spermatids with head and tail structures is greater for twine mutation than for pelo1, other pelota alleles, generated by remobilization of the pelo1 P element have a phenotype identical to that of the twine allele. The tails of 4N spermatids elongate significantly and the nuclei form wedge-shaped heads. The heads are larger than in wild type, fail to cluster normally and are not attached to the tails (Eberhart, 1995).

A weaker class of pelota mutations, in which some meioses, albeit aberrant, occur, was also generated by mobilization of the pelo1 P element. Spermatids from weak pelota homozygotes commonly contain two or four nuclei in a single cell, indicating a failure of cytokinesis in one or both meiotic divisions. Variations in nuclear size, reflecting defects in chromosome segregation, are also seen. Defects within a given cyst are usually heterogeneous, with some cells displaying meiotic defects while others appear wild type or are arrested before meiosis I (Eberhart, 1995).

In summary, during spermatogenesis, the mitotic divisions and subsequent growth phase appear normal in pelota mutants. The first apparent defect is a failure of meiotic cell division, resulting in the accumulation of arrested spermatocytes. The cell cycle arrest occurs early in meiosis; no metaphase or anaphase figures can be seen. Some aspects of spermiogenesis continue, resulting in 4N spermatids with head and tail structures, a phenotype identical to twine mutants (Eberhart, 1995).

To define the arrest point of pelota in greater detail, three landmark events occurring at meiosis I were analyzed: chromosome condensation, spindle formation and nuclear envelope breakdown. The analysis of the pelota mutant phenotype was facilitated by similar studies on twine and by a detailed description of chromosome and microtubule movements in spermatogenesis. During the spermatocyte growth phase leading up to meiosis, the two autosomes in each spermatocyte nucleus are visible as diffuse, mesh-like structures, while the sex chromosomes are associated with the nucleolus and often appear more punctate. Chromosome condensation occurs rapidly late in prophase; chromosomes condense on the periphery of the nucleus, compacting until they appear as dots. After the chromosomes have fully condensed they move inward to the center of the nucleus, appearing as a single mass. In arrested pelota spermatocytes, the chromosomes partially condense, but never move away from the nuclear periphery. The same levels of DNA condensation are observed in arrested twine spermatocytes (Eberhart, 1995).

A second critical meiotic event is nuclear envelope breakdown. The nuclear lamins are associated with the nuclear envelope in mature spermatocytes. During meiosis, the nuclear envelope breaks down and nuclear lamins disperse, forming diffuse clouds around the chromatin; after meiosis the nuclear lamins associate with the reformed nuclear envelope. As spermatids continue to develop, nuclear lamin staining is lost. The nuclear envelope does not break down in arrested pelota spermatocytes. In strong pelota alleles, heavy nuclear staining is seen in spermatocytes whose condensed chromosomes indicate they have just arrested in late meiotic prophase. Nuclear lamin staining is still present after the nebenkerne form. In pelota 4N spermatids that develop shaped head structures and elongate tails, lamin staining becomes fragmented and disappears. The fate of nuclear lamins in twine resembles that in pelota: the nuclear envelope remains intact at the initial arrest, the nuclear lamins are then degraded in conjunction with sperm head and tail formation (Eberhart, 1995).

Formation of the spindle is a third event central to meiotic cell division. During the spermatocyte growth phase, microtubules form a diffuse cytoplasmic network; this network persists until the cells mature. Late in meiotic prophase the centrosomes separate and move toward the poles; after they reach the poles the cytoplasmic tubulin network breaks down and a spindle is formed. In arrested pelota spermatocytes, the microtubules remain in the cytoplasm. The centrosomes separate, but don't complete their migration and nucleate no significant asters; a spindle is never observed. An identical phenotype is reported for twine mutants (Eberhart, 1995).

These studies indicate that spermatogenesis in pelota and twine homozygotes is normal until late meiotic prophase, at which point the cell cycle arrests. No spindles form in these mutants and the nuclear lamins do not disperse or degrade until significant spermatid differentiation has occurred. Not all meiotic events are blocked, however, since some chromosome condensation is seen. Cytoplasmic structures that in wild type form after meiosis (such as nebenkerne, shaped heads and elongated tails) develop in these 4N spermatids (Eberhart, 1995).

pelota mutants have defective eye morphogenesis

In flies homozygous for strong pelota alleles, the eyes are often rough, with disordered ommatidial arrays and bristles. In addition, the eyes of pelota homozygotes are up to 30% smaller than those of heterozygous siblings. The severity of the eye defects varies between flies: some homozygotes have eyes that appear wild type. These results demonstrate that pelota is required for Drosophila eye development (Eberhart, 1995).

Pelota controls self-renewal of germline stem cells by repressing a Bam-independent differentiation pathway

dpp overexpression in inner sheath cells driven by the c587-gal4 driver has been shown to completely block germ cell differentiation, resulting in the formation of GSC-like tumors and consequently female sterility (Song, 2004). Such female sterility is very sensitive to genetic changes of any dpp downstream components; for example, removal of one copy of any Bmp downstream gene such as punt, mad and Med can sufficiently reverse the sterility phenotype, leading to fertile females. To identify the genes that are potentially involved in Bmp signaling in GSCs, a dominant suppressor screen was conducted using the existing deficiency kit, which covers 65% of the Drosophila genome. In the screen, a small deficiency [ Df(2L)s1402 (30C-30F)] was identified that can rescue dpp overexpression-induced female sterility. Among 19 existing mutations in the genomic region, pelota is identified as dominantly suppressing dpp overexpression-induced sterility. Although it has been identified for its role in Drosophila male meiosis, its mutant females are also semi-fertile, and ovaries are overtly small (Eberhart, 1995), suggesting that it is also involved in the regulation of Drosophila oogenesis. However, it remains unclear whether the pelo mutation affects GSCs (Xi, 2005).

To determine if pelo is required for maintaining GSCs, GSCs were quantitated in pelo1 homozygous mutant germaria. pelo1 is a P-element-induced strong or null allele, which is based on the evidence that it produces a truncated pelo transcript deleting most of the eRF1alpha domain (Eberhart, 1995). The ovaries from 2-day-old or 7-day-old pelo1 homozygous and heterozygous females were immunostained with anti-Vasa and anti-Hts antibodies. Vasa is expressed specifically in germ cells, while Hts is preferentially rich in spectrosomes (GSCs and cystoblasts), fusomes (2-, 4-, 8- and 16-cell germline cysts) and membranes of somatic follicle cells in the germarium and egg chambers. GSCs can be reliably identified at the tip of the germarium by their anteriorly localized spectrosome and direct contact with cap cells. In pelo1 heterozygous control females, 2-day-old and 7-day-old germaria had an average of 2.35 and 2.40 GSCs, respectively, and more than 97% of the germaria contained two or more GSCs, which closely resembles wild-type. The 2-day-old pelo1 homozygous germaria contained an average of 1.4 GSCs, with some having two GSCs and others containing only one, indicating that pelo is required for GSC establishment or GSC maintenance. Furthermore, the 7-day-old pelo1 germaria had an average of 0.47 GSCs with 57.3% (51/89) of them containing no GSC. Consistent with the previous study showing that pelo1 is a strong or null allele (Eberhart, 1995), the pelo1/df(2L)s1402 mutant ovaries behaved just like the homozygous pelo1 mutant ovaries in terms of GSC numbers at different ages. This also suggested that the mutation in pelo is responsible for GSC loss phenotype in the pelo1 homozygous mutant ovaries. Together, these results demonstrate that Pelo is required for maintaining GSCs in the Drosophila ovary (Xi, 2005).

Pelo could maintain GSCs by controlling either self-renewal or survival. Thus, the GSC loss in pelo mutant ovaries could be due to either differentiation or cell death. To differentiate these two possibilities, cell death of GSCs was examined in the pelo mutant ovaries using the ApoTag cell death labeling system, which has been successfully used in previous studies (Zhu, 2003). In this experiment, the spectrosomes and fusomes were also labeled for facilitating identification of GSCs, cystoblasts and germline cysts. Among 156 pelo1 heterozygous control germaria, no dying GSCs (>250 GSCs examined) were observed, and there were eight dying cysts. This is consistent with the previous result that some germline cysts die naturally (Drummond-Barbosa, 2001). Among 264 pelo1 homozygous germaria, there were also no dying GSCs detected (>300 GSCs examined) but 49 dying cysts were observed. Clearly, the pelo mutation does not affect GSC survival but appears to increase dying cysts [from 5% of the 2-day-old wild-type germaria carrying dying cysts (n=40) to 18% of the 2-day-old pelo1 mutant garmaria carrying dying cysts (n=89)]. These observations suggest that Pelo is required for GSC self-renewal and also for cyst survival (Xi, 2005).

It was also noticed that the pelo mutant germaria that still harbor two GSCs were extremely small and contained very few germline cysts. Since the pelo mutation results in only 18% of the germaria carrying one or more dying cysts, the pelo mutant GSC division rate probably also decreased. Then, BrdU incorporation was used to label S-phase cells to determine whether pelo is required for controlling GSC division. In the 2-day-old females, 10.7% of pelo heterozygous control GSCs were BrdU positive, whereas only 2.5% of pelo homozygous GSCs incorporated BrdU. This result shows that pelo is also required for controlling GSC division (Xi, 2005).

Pelo could control GSC self-renewal by acting either inside the GSC, in the niche, or in both. mRNA in situ hybridization and gene expression profiles of agametic ovaries show that pelo mRNAs were ubiquitously expressed at lower levels throughout the germarium, suggesting that pelo could function in GSCs or the somatic niche cells, or both. FLP-FRT-mediated mitotic recombination was used to determine whether Pelo functions inside GSCs for controlling their self-renewal. The FLP-mediated FRT recombination has been used to generate marked mutant GSCs and determine their loss rates for deducing the role of a particular gene in GSC maintenance (Xie, 1998). According to published experimental procedures (Xie, 1998; Song, 2002a), the ovaries of the females of appropriate genotypes were dissected at 3, 10, 17 and 24 days after clone induction (ACI) mediated by heat-shock treatments, and marked wild-type and pelo mutant GSCs were identified by the lack of arm-lacZ expression and the presence of an anteriorly anchored spectrosome. In the wild-type control, 55.0% of the marked GSCs (from 52.8% of the germaria carrying one or more marked control GSCs at 3 days ACI to 28.9% of the germaria carrying one or more marked control GSCs at 24 days ACI) were still maintained for 3 more weeks (Xie, 1998). By contrast, 97% of the marked pelo mutant GSCs (from 48.6% of the germaria carrying one or more marked mutant GSCs at 3 days ACI to 1.7% of the germaria carrying one or more marked mutant GSCs at 24 days ACI) were lost during the same three week period. These results demonstrate that pelo is required in GSCs for controlling their self-renewal. It appears that these marked pelo mutant GSCs are lost slower than the GSCs in the homozygous pelo mutant ovaries. This could be explained by the possibility that Pelo is very stable or has functions in both GSCs and soma. If Pelo is very stable, it takes longer for residual wild-type Pelo that is made before clone induction to be degraded in the marked pelo mutant GSCs (Xi, 2005).

To confirm further that Pelo is indeed required intrinsically for controlling GSC self-renewal and that the pelo mutation is responsible for the GSC loss phenotype, a UASp-pelo transgene was expressed specifically in the germ cells using a germ cell-specific GAL4 driver, nos-gal4VP16, in pelo mutant ovaries. A UASp-pelo construct was made to be expressed in germline or soma using different GAL4 drivers; nosgal4-VP16 can drive a UAS transgene to be expressed in both GSCs and later germ cell cysts. Interestingly, introduction of one copy of UASp-pelo transgene alone into the pelo homozygous females was able to partially rescue the GSC loss phenotype, suggesting that there is a leaky expression of the transgene even without a GAL4 driver. The stem cell loss phenotype in pelo mutant ovaries was fully rescued by nosgal4VP16-driven pelo expression in the germline, including GSCs, restoring the normal GSC number. This result shows that the mutation in pelo is responsible for the GSC loss phenotype, and further confirms that pelo is required intrinsically for controlling GSC self-renewal (Xi, 2005).

Although pelo is required intrinsically for controlling GSC self-renewal, it does not rule out the possibility that a somatic function of pelo is also involved in regulating GSC self-renewal since it is also expressed in the somatic cells of the germarium. Initially, whether the pelo mutation affects the survival of cap cells was examined. A hh-lacZ enhancer trap line used in this study has been used to label terminal filament cells and cap cells in the Drosophila ovary. In the pelo homozygous germaria carrying one or no GSCs, the cap cell number appeared to be normal, ranging from five to seven, indicating that Pelo function is at least not required for the formation or survival of cap cells. However, pelo could still be required in the surrounding somatic cells for controlling GSC function through regulating production of signals. To further test whether pelo has a somatic function in GSC regulation, the c587-gal4 driver, which is expressed in IGS cells and follicle progenitor cells, and the same UASp-pelo transgene were used to test whether somatic expression pelo can rescue the pelo mutant GSC loss phenotype. However, c587-driven pelo expression in the somatic cells could only confer very limited rescue of the pelo mutant GSC loss phenotype, in addition to the partial rescue conferred by the UAS-pelo transgene alone, suggesting that pelo has little role in IGS cells and follicle cell progenitors for GSC self-renewal. It has not been tested whether pelo expression in terminal filaments/cap cells can mitigate the GSC loss phenotype of the pelo mutant ovaries; the results can not completely rule out the possibility that Pelo has a function in somatic cells for controlling GSC self-renewal (Xi, 2005).

Since pelo is expressed in all the somatic cells, including SSCs, whether pelo has a role in SSC maintenance was tested using FLP-mediated FRT recombination to generate marked pelo mutant SSC clones. The marked SSCs were identified as the arm-lacZ-negative somatic cells residing at the 2a/2b boundary and generating arm-lacZ-negative (marked) follicle cells in the germarium and egg chambers, according to previous studies (Song, 2002a; Song, 2003). In the control, 68% of marked wild-type SSCs were maintained for 3 weeks, supporting the fact that SSCs have a slow natural turnover. Similarly, 62% of the marked pelo SSCs were maintained for 3 weeks, indicating that pelo plays little or no role in SSC maintenance. The marked pelo1 mutant follicle cell clones exhibited a very minor phenotype: they appeared slightly thinner compared with wild-type follicle cells. Although pelo is ubiquitously expressed throughout the germarium, the main function of pelo is primarily restricted to GSCs and their progeny in the ovary (Xi, 2005).

Drosophila Pelo has a putative nuclear localization signal sequence (PRKRK) at its N terminus; this sequence is perfectly conserved from Drosophila to human, raising an interesting possibility that Pelo is a nuclear protein. If Pelo indeed functions in the nucleus, it would be expected that the disruption of the putative nuclear localization sequence would lead to loss of its function. To directly test the idea, a mutant version of Pelo was generated with the replacement of PRKRK by RSRS, since ablation of helix-breaking residue proline and reduction of basic residues can abolish the function of the nuclear localization signal. In S2 cells, the mutant Pelo protein tagged with 3xFlag and 6xMyc at its N terminus [F-M-Pelo(nls*)] was localized in the cytoplasm in the same way as the wild-type version tagged with the same tags at its N terminus (F-M-Pelo). To further determine whether the NLS of Pelo is important for Pelo function in controlling GSC self-renewal in vivo, transgenic flies were generated carrying either UASp-F-M-Pelo or UASp-F-M-Pelo(nls*). Two independent insertion lines for UAS-F-M-Pelo could fully rescue the pelo mutant GSC loss phenotype when they were driven to be expressed specifically in the germ cells by nos-gal4VP16, indicating that FLAG and MYC tags do not interfere with Pelo function. Similarly, two independent transgenic lines of the NLS mutated version of Pelo could also fully rescue the pelo GSC loss phenotype, further supporting that the putative NLS is not important for Pelo function in GSCs and that Pelo functions in the cytoplasm to control GSC self-renewal. Interestingly, one of the transgenic lines [UASp-FM(nls*)#1] showed complete rescue for the pelo GSC loss phenotype with the nosgal4VP16 driver, whereas it exhibited little rescue for the GSC loss phenotype of the pelo mutant ovaries with the c587 driver or without any gal4 driver, further supporting the earlier conclusion that the mutation in the pelo gene is responsible for the GSC loss (Xi, 2005).

Since the tagged Pelo is functional, the Pelo subcellular localization in GSCs was determined using Flag or Myc antibodies. As in S2 cells, Pelo is mainly expressed in the cytoplasm in the germ cells. Since Pelo protein has a domain showing homology to translation release factor 1a (RF1), whether Pelo is associated with the ER was examined. Sec61alpha-GFP, a GFP fusion protein localized to ER membrane, is localized to ER membrane rich in the peri-nuclear area and spectrosome area of the GSC, while Pelo is evenly distributed throughout the cytoplasm of the GSC. There was only limited pattern overlap between Sec61alpha-GFP and F-M-Pelo, indicating that Pelo is primarily localized to the cytoplasm away from the ER membrane. Consistently, Pelo was also localized to the cytoplasm in S2 cells. These findings show that Pelo functions in the cytoplasm of GSCs to control their self-renewal (Xi, 2005).

It was noticed that the pelo mutant females have some fertility after eclosion and quickly loose their fertility. Interestingly, in the 2-day-old pelo mutant ovaries, early egg chambers look largely normal, and even a few mature eggs are present. By contrast, in the 7-day-old ovaries, egg chambers older than stage 9 are rarely observed, and even those early stage egg chambers exhibit condensed nurse cell DNA: this suggests that the egg chambers are in the process of undergoing apoptosis. The egg chamber degeneration is not due to oocyte formation defect because in these egg chambers the oocyte is present. In addition, the size of some egg chambers exhibiting condensed nurse cell DNA is also smaller than normal. The Pelo function also appears to be germ-cell specific in egg chambers, since marked mutant pelo germ cells fail to grow to the normal size and become apoptotic. These results indicate that pelo is also required in the germ cells for their survival or normal differentiation during later oogenesis (Xi, 2005).


Pelota homologs in bacteria and yeast

An open reading frame (pelA) specifying a homolog of pelota and DOM34, proteins required for meiotic cell division in Drosophila melanogaster and Saccharomyces cerevisiae, respectively, has been cloned, sequenced and identified from the archaebacterium Sulfolobus solfataricus. The S. solfataricus PelA protein is about 20% identical with pelota, DOM34 and the hypothetical protein R74.6 of Caenorhabditis elegans. The presence of a pelota homolog in archaebacteria implies that the meiotic functions of the eukaryotic protein were co-opted from, or added to, other functions existing before the emergence of eukaryotes. The nuclear localization signal and negatively charged carboxy-terminus characteristic of eukaryotic pelota-like proteins are absent from the S. solfataricus homolog, and hence may be indicative of the acquired eukaryotic function(s) (Ragan, 1996).

The DOM34 gene of Saccharomyces cerevisiae is similar to genes found in diverse eukaryotes and archaebacteria. Analysis of dom34 strains shows that progression through the G1 phase of the cell cycle is delayed, mutant cells enter meiosis aberrantly, and their ability to form pseudohyphae is significantly diminished. RPS30A, which encodes ribosomal protein S30, was identified in a screen for high-copy suppressors of the dom34delta growth defect. dom34delta mutants display an altered polyribosome profile that is rescued by expression of RPS30A. Taken together, these data indicate that Dom34p functions in protein translation to promote G1 progression and differentiation. A Drosophila homolog of Dom34p, pelota, is required for the proper coordination of meiosis and spermatogenesis. Heterologous expression of pelota in dom34delta mutants restores wild-type growth and differentiation, suggesting conservation of function between the eukaryotic members of the gene family (Davis, 1998).

G proteins, which bind and hydrolyze GTP, are involved in regulating a variety of critical cellular processes, including the process of protein synthesis. Many members of the subfamily of elongation factor class G proteins interact with the ribosome and function to regulate discrete steps during the process of protein synthesis. Despite sequence similarity to factors involved in translation, a role for the yeast Hbs1 protein has not been defined. In this work, a genetic relationship has been identified between genes encoding components of the translational apparatus and HBS1. HBS1, while not essential for viability, is important for efficient growth and protein synthesis under conditions of limiting translation initiation. The identification of an Hbs1p-interacting factor, Dom34p, which shares a similar genetic relationship with components of the translational apparatus, suggests that Hbs1p and Dom34p may function as part of a complex that facilitates gene expression. Dom34p contains an RNA binding motif present in several ribosomal proteins and factors that regulate translation of specific mRNAs. Thus, Hbs1p and Dom34p may function together to help directly or indirectly facilitate the expression either of specific mRNAs or under certain cellular conditions (Carr-Schmid, 2002).

Pelota homolog in mammals

The pelota gene of Drosophila encodes a protein that was found to be included in cell cycle regulation. Mutations were found to result in spermatogenic arrest, female sterility and disturbances in the patterning of the eye. The human pelota cDNA (PELO) encodes a 385-amino-acid protein. Southern blot and fluorescence in situ hybridization analyses revealed that PELO is present as a single copy gene in the human genome and is localized on chromosome 5q11.2. Northern blot analysis revealed the presence of a 1.6-kb transcript in all tissues studied and an additional 2.0-kb transcript in testis (Shamsadin, 2000).

The pelota gene of Drosophila encodes a protein which is included in cell cycle regulation. Mutations were found to result in spermatogenic arrest, female sterility and disturbances in the patterning of the eye. cDNA clones coding for the human pelota gene (PELO) have been identified. The murine pelota cDNA and gene (Pelo) encodes a 385-amino-acid protein. The exon-intron structure of the gene, which contains three exons, was determined. Comparison of the mouse amino acid sequences with the human and Drosophila sequences revealed an overall high identity (96% and 70%, respectively). Northern blot analysis detected a 1.7-kb transcript in all tissues studied. Southern blot analyses revealed that the pelota gene is present as a single copy in the mouse genome. The mouse pelota gene (Pelo) was mapped to the distal end of chromosome 13, in a region that is homologous with a segment of human chromosome 5q11 containing the orthologous human gene. Cloning of the mouse gene is an important step to study the function of the pelota gene in mammals and to create a mouse model for this evolutionarily conserved gene (Shamsadin, 2002).

Mutations in either the Drosophila pelota or pelo gene or the Saccharomyces cerevisiae homologous gene, DOM34, cause defects of spermatogenesis and oogenesis in Drosophila, and delay of growth and failure of sporulation in yeast. These phenotypes suggest that pelota is required for normal progression of the mitotic and meiotic cell cycle. To determine the role of the pelota in mouse development and progression of cell cycle, a targeted disruption of the mouse PELO was established: heterozygous animals are variable and fertile. Genotyping of the progeny of heterozygous intercrosses shows the absence of Pelo-/- pups and suggests an embryo-lethal phenotype. Histological analyses reveal that the homozygous Pelo deficient embryos fail to develop past day 7.5 of embryogenesis (E7.5). The failure of mitotic active inner cell mass of the Pelo-/- blastocysts to expand in growth after 4 days in culture and the survival of mitotic inactive trophoplast indicate that the lethality of Pelo-null embryos is due to defects in cell proliferation. Analysis of the cellular DNA content reveals the significant increase of aneuploid cells in Pelo-/- embryos at E7.5. Therefore, the percent increase of aneuploid cells at E7.5 may be directly responsible for the arrested development and suggests that Pelo is required for the maintenance of genomic stability (Adham, 2003).


Search PubMed for articles about Drosophila Pelota

Adham, I. M., et al. (2003). Disruption of the pelota gene causes early embryonic lethality and defects in cell cycle progression. Mol. Cell. Biol. 23(4): 1470-6. 12556505

Carr-Schmid, A., Pfund, C., Craig, E. A. and Kinzy, T. G. (2002). Novel G-protein complex whose requirement is linked to the translational status of the cell. Mol. Cell. Biol. 22: 2564-2574. 11909951

Chen, D. and McKearin, D. (2003a). Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells. Curr. Biol. 13: 1786-1791. 14561403

Chen, D. and McKearin, D. (2003b). A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell. Development 130: 1159-1170. 12571107

Chen, D. and McKearin, D. (2005). Gene circuitry controlling a stem cell niche. Curr. Biol. 15: 179-184. 15668176

Cox, D. N., Chao, A. and Lin, H. (2000). piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 127: 503-514. 10631171

Davis, L. and Engebrecht, J. (1998). Yeast dom34 mutants are defective in multiple developmental pathways and exhibit decreased levels of polyribosomes. Genetics 149: 45-56. 9584085

Drummond-Barbosa, D. and Spradling, A. C. (2001). Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev. Biol. 231: 265-278. 11180967

Eberhart, C. G. and Wasserman, S. A. (1995). The pelota locus encodes a protein required for meiotic cell division: an analysis of G2/M arrest in Drosophila spermatogenesis. Development 121(10): 3477-86. 7588080

Huh, W. K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S. and O'Shea, E. K. (2003). Global analysis of protein localization in budding yeast. Nature 425: 686-691. 14562095

King, F. J., Szakmary, A., Cox, D. N. and Lin, H. (2001). Yb modulates the divisions of both germline and somatic stem cells through piwi- and hh-mediated mechanisms in the Drosophila ovary. Mol. Cell 7: 497-508. 11463375

Lin, H. (2002). The stem-cell niche theory: lessons from flies. Nat. Rev. Genet. 3: 931-940. 12459723

Ragan, M. A., et al. (1996). An archaebacterial homolog of pelota, a meiotic cell division protein in eukaryotes. FEMS Microbiol. Lett. 144(2-3): 151-5. 8900058

Shamsadin, R., Adham, I. M., von Beust, G. and Engel, W. (2000). Molecular cloning, expression and chromosome location of the human pelota gene PELO. Cytogenet. Cell Genet. 90(1-2): 75-8. 11060452

Shamsadin, R., Adham, I. M. and Engel, W (2002). Mouse pelota gene (Pelo): cDNA cloning, genomic structure, and chromosomal localization. Cytogenet. Genome Res. 97(1-2): 95-9. 12438745

Song, X., Zhu, C. H., Doan, C. and Xie, T. (2002a). Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 296: 1855-1857. 12052957

Song, X. and Xie, T. (2002b). DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary. Proc. Natl. Acad. Sci. 99: 14813-14818. 12393817

Song, X. and Xie, T. (2003). Wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila. Development 130: 3259-3268. 12783796

Song, X., Wong, M. D., Kawase, E., Xi, R., Ding, B. C., McCarthy, J. J. and Xie, T. (2004). Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development 131: 1353-1364. 14973291

Szakmary, A., Cox, D. N., Wang, Z. and Lin, H. (2005). Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation. Curr. Biol. 15: 171-178. 15668175

Xi, R., Doan, C., Liu, D. and Xie. T. (2005). Pelota controls self-renewal of germline stem cells by repressing a Bam-independent differentiation pathway. Development 132(24): 5365-74. 16280348

Xie, T. and Spradling, A. (1998). decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell 94: 251-260. 9695953

Xie, T. and Spradling, A. (2000). A niche maintaining germ line stem cells in the Drosophila ovary. Science 290: 328-330. 11030649

Xie, T. and Spradling, A. (2001). The Drosophila ovary: an in vivo stem cell system. In Stem Cell Biology (ed. D. R. Marshak R. L. Gardner and D. Gottlieb), pp. 129-148. New York: Cold Spring Harbor Laboratory Press. FlyBase report: FBrf0137009

Zhu, C. H. and Xie, T. (2003). Clonal expansion of ovarian germline stem cells during niche formation in Drosophila. Development 130: 2579-2588. 12736203

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date revised:30 March 2006

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