You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Xu Yang + 2349 word(s) 2349 2021-05-08 04:46:16 |
2 format correct Karina Chen Meta information modification 2349 2021-05-19 11:07:24 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Yang, X. Sex Determination Cascade in Silkworm. Encyclopedia. Available online: https://encyclopedia.pub/entry/9788 (accessed on 19 December 2025).
Yang X. Sex Determination Cascade in Silkworm. Encyclopedia. Available at: https://encyclopedia.pub/entry/9788. Accessed December 19, 2025.
Yang, Xu. "Sex Determination Cascade in Silkworm" Encyclopedia, https://encyclopedia.pub/entry/9788 (accessed December 19, 2025).
Yang, X. (2021, May 18). Sex Determination Cascade in Silkworm. In Encyclopedia. https://encyclopedia.pub/entry/9788
Yang, Xu. "Sex Determination Cascade in Silkworm." Encyclopedia. Web. 18 May, 2021.
Sex Determination Cascade in Silkworm
Edit
This entry is adapted from the peer-reviewed paper 10.3390/genes12020315

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. 

sex determination cascade Lepidoptera insects silkworm

1. Introduction

The sex determination pathways in insects are diverse [1]. The diversity arises mostly from primary signals, whereas transducers and executors are more conserved [2][3]. In D. melanogaster, M. domestica and C. capitata the primary sex determiner controls sex development via Tra-transduced signaling pathway, resulting in the alternative splicing of dsx [4][5][6]. The transducer gene usually encodes a splicing factor, and manipulation by the primary signals therefore exists or functions as a sex determiner only in one sex. The products of the executor gene dsx act downstream of these switches. There are female- and male-specific isoforms of DSX, which control sexual development in most insect species [7]. However, in the silkworm, the ortholog of tra does not exist, and no dsx cis-regulatory element binding sites are found, which indicates the sex determination pathways are markedly different from those seen in flies [8][9].

In the lepidopteran model species B. mori, the primary signal is the PIWI-interacting RNA (piRNA) Fem, which is derived from the W chromosome [10]. Fem silences a gene unique to Lepidoptera, Masc, which is essential for both male determination and repression of the vital process of dosage compensation of Z-linked genes during embryogenesis (Figure 1) [11][12][13][14][15]. In recent years, sex-determined factors encoded by PSI, Znf-2, Siwi and Gtsf1 have been identified along with preliminary established genetic cascade of the sex determination in the silkworm [16][17][18][13][19].

2. Feminizers, the Primary Signals

Research on sex determination factors in the silkworm began in 1933 when Hasimoto hypothesized that the F-factor originates from the W chromosome [20]. Subsequent genetic studies showed that one copy of the W chromosome is sufficient to determine femaleness [21]. However, in part due to the various transposable elements, their remnants, and simple repeats on W chromosome, the identity of the F-factor was a mystery [22][23]. Only recently was the F-factor identified when researchers used new generation sequencing technologies, bioinformatics and focused on non-coding RNAs (such as microRNAs, long non-coding RNAs and piRNAs). The F-factor is a single piRNA derived from a piRNA precursor named Fem, which is transcribed from the W chromosome. Fem functions as the primary determinant of female sex in the silkworm [10][24][25][26][27][28].

piRNAs are a class of small RNAs of 24–31 nucleotides in size. They are produced from transposons and from discrete genomic loci called piRNA clusters. The piRNAs guide PIWI proteins to target transcripts [29][30]. In flies, piRNAs and PIWI proteins mainly function in germ cells during gametogenesis to suppress transposable elements, which are selfish genomic elements that are able to jump around the genome [29][30]. It is fascinating that the Fem-derived piRNA participates in sex determination, which is a somatic cell fate event in the silkworm. The piRNA pathway is not well characterized in vivo, and as a result how Fem functions at the molecular level is still a puzzle [31]. piRNAs have no enzyme activity, and instead they assemble into piRNA-induced silencing complexes (piRISCs) with the PIWI proteins such as Siwi and Argonaute RISC Catalytic Component 3 (Ago3) identified in the silkworm [24]. After loading onto PIWI proteins, piRNAs are produced by a unique biogenesis pathway called the “ping-pong” cycle. The ping-pong cycle is a posttranscriptional gene-silencing mechanism in which RNAs degraded by piRNA-guided transcript silencing provide substrates for additional piRNA production [32]. We have discovered that SIWI is crucial for feminizing the silkworm, whereas Ago3 mutants display no phenotype involved in sex determination [16]. Our studies suggest that SIWI is dominant during Masc mRNA silencing via Fem-piRNA, whereas Ago3 have minor effects on Fem piRNA processing.

The demonstration that piRNAs have a function in sex determination in the silkworm prompted us try to understand the intricate biogenesis of PIWI-interacting RNAs. The sex determination cascades, as well as piRNA pathways, are distinct in D. melanogaster and B. mori [31]. The piRNA biogenesis pathway consists of a list of components which are specialized for their processing [33]. However, several key elements of the piRNA pathway in the fly, such as Yb, Rhino, Deadlock and Cutoff, which are crucial for piRNA transcription initiation and piRNA processing, are absent in the silkworm [33]. We have reported that a conserved component of the piRNA pathway called Gtsf1 is involved in female sex determination in the silkworm [18]. In Drosophila, Gtsf1 is required for female fertility and interacts with PIWI via its C-terminal end; and it is also essential for piRISCs-induced transposon silencing but not for piRNA biogenesis [34][35]. In the silkworm Gtsf1 is not only necessary for transposon silencing but also for piRNA biogenesis [18]. In addition, our co-immunoprecipitation experiments suggested that Gtsf1 interacts with SIWI. Such an interaction was also observed in Drosophila [18][34][35]. Interestingly, not every component from the piRNA pathway participates in feminization. For instance, Maelstrom (Mael) is essential for spermatogenesis and oocyte development in Drosophila as it is involved in piRNA-mediated silencing of transposable elements [36]. However, depletion of Mael in the silkworm leads to spermatogenesis defects but does not affect sexual development [37]. The poly(A)-specific ribonuclease-like domain-containing (Pnldc1) is necessary for piRNA maturation in silkworms, and mutation of Pnldc1 leads to abnormalities in nuclei of cells in eupyrene sperm bundles but not cells of other organs [38][39]. We have generated transgenic lines using CRISPR-Cas9 technology with mutations in Zucchini and Papi, which encode enzymes required for 3’-end processing of piRNAs, in Tdrd12 and Tudor-SN, which are involved in ping-pong cycling, and in Yu, Armi and Mino, which encode chaperonins that function during piRNAs biogenesis, but none of these lines exhibit any obvious phenotypes (unpublished data). However, all these genes are crucial for piRNA processing in Drosophila, and their mutation will cause sterility, whereas our results indicate that the piRNA processing pathway is also different between silkworms and flies, and the processing of the primary signal Fem-piRNA is independent of those elements [33]. Furthermore, we do not understand how Fem transcription is activated, and it is possible that piRNAs other than Fem or non-coding RNAs from W are involved in sex determination. If other non-coding RNAs from W are involved in the female sex determination of B. mori, their role is expected to be minor if compared with Fem. Indeed, Fem repression is sufficient to cause masculinization of dsx splicing in embryos.

3. Masculinizers, the Possible Transducers

Masc is the target gene of the primary signal mediated by Fem [10]. Evolutionary analysis revealed that Masc is conserved among the species in Lepidoptera but is not found in other insects, indicating that the sex determination pathway in Lepidoptera is likely distinct [40]. In the silkworm, Masc is located on the Z chromosome [10]. It encodes a CCCH-tandem zinc-finger protein and controls both masculinization and dosage compensation [41]. Recent studies have demonstrated that Masc is also required for masculinization in multiple lepidopterans including Trilocha varians, Ostrinia furnacalis and Agrotis ipsilon [11][14][15]. Besides, it is interesting that in O. furnacalis, Wolbachia-induced male-specific lethality is also caused by a failure of dosage compensation via suppression of Masc [42]. However, it remains to be determined whether Masc functions as masculinizer among all the species in the Lepidoptera order. A novel splice variant of Masc (Masc-S), which lacks the intact sequence of the cleavage site for Fem-piRNA, encodes a C-terminal truncated protein that has been identified in both sexes. The variant of Masc, Masc-S, participates in female genital development in the silkworm [43]. Moreover, there is still a gap between Masc and dsx, and further investigations that identify the direct targets of Masc will be able to clarify its role.

In Drosophila females, female-specific dsx is promoted by Tra and Tra-2 as trans-acting splicing activators [4][2] (Figure 1E). In Bombyx, lacking tra ortholog, the sex-specific splicing regulation of the dsx gene is different (Figure 1F). A splicing factor might have replaced the function as Tra in transformer-less species during evolution [44][45][46]. PSI is a KH-domain RNA-binding splicing factor that regulates tissue-specific alternative splicing of P-element transposon transcripts to restrict transposition activity to germ-line tissues and that influences development and mating behavior in flies [47][48][49][50][51][52]. Though PSI is not involved in the sex determination pathway in Drosophila, it is a key auxiliary factor in silkworm male sex determination. PSI binds to exon 4 of dsx pre-mRNA and facilitates its male-specific splicing [19]. Genetic evidence, by using a transgenic CRISPR/Cas9 system, has shown that the mutation of PSI will cause partial male-to-female defects, whereas it has been demonstrated that it is indispensable for masculinization in the silkworm [13]. It is still unclear that PSI affects only males, however, as it is present in both sexes. Besides, according to published reference genomes, PSI is present in multiple lepidopterans, but whether it is involved in sex determination still remains to be identified [53]. Recently, it was reported that a Znf-2 mutant has a phenotype similar to that of the PSI loss-of-function mutant [17]. Znf-2 encodes a CCCH-type zinc finger protein and contributes to male-specific splicing of dsx in silkworm cell lines [54]. The Znf-2 mutant males have feminized external genitalia, and the female isoform of dsx is detected in males, indicating that Znf-2 is essential for male sexual differentiation [17]. In addition, larval development is delayed and body size diminished in PSI and Znf-2 mutant males, demonstrating that these factors have functions in development in the silkworm.

Genes 12 00315 g002 550

Figure 1. Comparison of the sex determination cascade between Drosophila melanogaster (A,C,E) and Bombyx mori (B,D,F). In female D. melanogaster, the dosage of several X-linked signal element proteins regulates the transcription initialization of Sex-lethal (Sxl). An autoregulatory feedback loop ensures continuous expression. Methyltransferase complex components also regulate the precise splicing of Sxl (A) [55][56][57][58]. The Sxl protein (SXL) directly binds to transformer (tra) pre-mRNA and regulates its alternative splicing. Male-specific-lethal 2 (Msl2) is inhibited at the mRNA level (C). Functional transformer protein (TRA) with transformer-2 protein (TRA2) together regulate doublesex (dsx) female-specific alternative splicing (E) [4]. The female-specific DSX (DSXF) interacts with Intersex protein (IX) to promote female development [59]. In female B. mori, the Feminizer piRNA (Fem) derived from the female W chromosome is postulated to interact with the protein Silkworm-PIWI (SIWI) and gametocyte-specific factor 1 (GTSF1) to form the piRNA-induced silencing complexes that silences Masculinizer (Masc) at the mRNA level (B) [10][16][18]. In male B. mori, the Masc protein (MASC) increases the expression of Bombyx mori dsx RNA-binding protein 3 (RxRBP3) (D). RxRBP3, together with the protein of P-element somatic inhibitor (PSI), regulates the male-specific alternative splicing of dsx (F) [12][60][61][62]. The male-specific DSX (DSXM) promotes male development [63][64].

There is strong evidence supporting that Masc, PSI and Znf-2 are indispensable for masculinization, but where and how exactly these factors function in the sex determination cascade is not known. These questions may be answered by dissection of the functional relationships among Masc, PSI and Znf-2, and by identification of additional players in the sex determination pathway. Recent studies have identified components as BxRBP1, BxRBP2 and BxRBP3 (Bombyx mori dsx RNA-binding proteins) are dsx pre-mRNA binding protein by using the strategy of yeast three-hybrid screening. It is interesting that the alternatively transcribed BxRBP3 isoforms are regulated by Masc and physically interact with PSI, but whether BxRBP3 is the transducer remains to be verified via genetic methods [60] (Figure 1D,F). However, based on the observation that females can be completely reversed to males when the signal transducer tra is knocked-down or knocked-out in Diptera, we speculate that the transducer in the silkworm either has not yet been identified or may act very differently in the sex determination cascade [65][66][67][68][69].

4. Doublesex, the Executor

DSX protein sex-specific isoforms are conserved in insects and act as the downstream regulator in the sex determination pathway [7]. DSX controls sexual dimorphic development in insects, and mutation of sex-specific isoforms will cause male or female reproductive defects, respectively; hence, it has been targeted in development of sterile insect biotechnology [70][71][72][73]. As in Diptera, also in Lepidoptera, the dsx pre-mRNA is alternatively spliced to encode transcription factors that contain a common N-terminal domain and a sex-specific C-terminal domain [74]. The N-terminal domain possesses a DNA-binding motif that mediates the binding of DSX to target genes, whereas the C-terminal domain is crucial for DSX regulation of sexual development [63][75]. Disruptions of functions of certain isoforms of DSX lead to either sex-specific sexual-dimorphic defects or intersexual phenotypes in multiple Lepidoptera insects including B. mori, A. ipsilon, Plutella xylostella and H. cunea [64][76][77][78].

In Drosophila, the transcription cofactor Intersex (Ix) functions together with the female-specific product of dsx, DSXF, to implement female sexual differentiation [59] (Figure 1E). However, depletion of ix in the silkworm does not affect gonad development or splicing of the dsx pre-mRNA in either sex, suggesting that ix functions differently in silkworms than in flies [61]. The transcription factor Fruitless (Fru) plays roles in sexual behaviors and is regulated by the sex determination cascade in flies [79]. A recent study in the silkworm demonstrated that Fru is also affected by the upstream sex-determining factors and acts together with DSX to regulate both mating and courtship behavior [80].

Although DSX exists in the majority of insect species, the mechanisms by which it functions in sex determination and subsequent developmental processes are poorly understood in most insect species. Only a few genes directly controlled by DSX have been identified, although numerous targets of DSX have been predicted and analyzed on the genome-wide scale in Drosophila [81][82]. It remains to be determined whether the events downstream of DSX were conserved among insects during evolution [83].

References

  1. Bachtrog, D.; Mank, J.E.; Peichel, C.L.; Kirkpatrick, M.; Otto, S.P.; Ashman, T.L.; Hahn, M.W.; Kitano, J.; Mayrose, I.; Ming, R.; et al. Sex Determination: Why So Many Ways of Doing It? PLoS Biol. 2014, 12, e1001899.
  2. Verhulst, E.C.; van de Zande, L.; Beukeboom, L.W. Insect sex determination: It all evolves around transformer. Curr. Opin. Genet. Dev. 2010, 20, 376–383.
  3. Sánchez, L. Sex-determining mechanisms in insects. Int. J. Dev. Biol. 2008, 52, 837–856.
  4. Salz, H.K.; Erickson, J.W. Sex determination in Drosophila: The view from the top. Fly (Austin) 2010, 4, 60–70.
  5. Sharma, A.; Heinze, S.D.; Wu, Y.; Kohlbrenner, T.; Morilla, I.; Brunner, C.; Wimmer, E.A.; Van De Zande, L.; Robinson, M.D.; Beukeboom, L.W.; et al. Male sex in houseflies is determined by Mdmd, a paralog of the generic splice factor gene CWC22. Science 2017, 356, 642–645.
  6. Meccariello, A.; Salvemini, M.; Primo, P.; Hall, B.; Koskinioti, P.; Dalíková, M.; Gravina, A.; Gucciardino, M.A.; Forlenza, F.; Gregoriou, M.E.; et al. Maleness-on-the-Y (MoY) orchestrates male sex determination in major agricultural fruit fly pests. Science 2019, 365, 1457–1460.
  7. Matson, C.K.; Zarkower, D. Sex and the singular DM domain: Insights into sexual regulation, evolution and plasticity. Nat. Rev. Genet. 2012, 13, 163–174.
  8. Geuverink, E.; Beukeboom, L.W. Phylogenetic distribution and evolutionary dynamics of the sex determination genes doublesex and transformer in insects. Sex. Dev. 2014, 8, 38–49.
  9. Traut, W.; Sahara, K.; Marec, F. Sex chromosomes and sex determination in Lepidoptera. Sex. Dev. 2007, 1, 332–346.
  10. Kiuchi, T.; Koga, H.; Kawamoto, M.; Shoji, K.; Sakai, H.; Arai, Y.; Ishihara, G.; Kawaoka, S.; Sugano, S.; Shimada, T.; et al. A single female-specific piRNA is the primary determiner of sex in the silkworm. Nature 2014, 509, 633–636.
  11. Wang, Y.H.; Chen, X.E.; Yang, Y.; Xu, J.; Fang, G.Q.; Niu, C.Y.; Huang, Y.P.; Zhan, S. The Masc gene product controls masculinization in the black cutworm, Agrotis ipsilon. Insect Sci. 2019, 26, 1037–1044.
  12. Sakai, H.; Sumitani, M.; Chikami, Y.; Yahata, K.; Uchino, K.; Kiuchi, T.; Katsuma, S.; Aoki, F.; Sezutsu, H.; Suzuki, M.G. Transgenic Expression of the piRNA-Resistant Masculinizer Gene Induces Female-Specific Lethality and Partial Female-to-Male Sex Reversal in the Silkworm, Bombyx mori. PLoS Genet. 2016, 12, e1006203.
  13. Xu, J.; Chen, S.; Zeng, B.; James, A.A.; Tan, A.; Huang, Y. Bombyx mori P-element Somatic Inhibitor (BmPSI) Is a Key Auxiliary Factor for Silkworm Male Sex Determination. PLoS Genet. 2017, 13, e1006576.
  14. Lee, J.; Kiuchi, T.; Kawamoto, M.; Shimada, T.; Katsuma, S. Identification and functional analysis of a Masculinizer orthologue in Trilocha varians (Lepidoptera: Bombycidae). Insect Mol. Biol. 2015, 24, 561–569.
  15. Fukui, T.; Kiuchi, T.; Shoji, K.; Kawamoto, M.; Shimada, T.; Katsuma, S. In vivo masculinizing function of the Ostrinia furnacalis Masculinizer gene. Biochem. Biophys. Res. Commun. 2018, 503, 1768–1772.
  16. Li, Z.; You, L.; Yan, D.; James, A.A.; Huang, Y.; Tan, A. Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination. PLoS Genet. 2018, 14, e1007245.
  17. Yang, F.; Zhang, Z.; Hu, B.; Yu, Y.; Tan, A. The role of Bmznf-2 in the silkworm. Insect Sci. 2020, 1–44.
  18. Chen, K.; Yu, Y.; Yang, D.; Yang, X.; Tang, L.; Liu, Y.; Luo, X.; Walter, J.R.; Liu, Z.; Xu, J.; et al. Gtsf1 is essential for proper female sex determination and transposon silencing in the silkworm, Bombyx mori. PLoS Genet. 2020.
  19. Suzuki, M.G.; Imanishi, S.; Dohmae, N.; Nishimura, T.; Shimada, T.; Matsumoto, S. Establishment of a Novel In Vivo Sex-Specific Splicing Assay System To Identify a trans-Acting Factor That Negatively Regulates Splicing of Bombyx mori dsx Female Exons. Mol. Cell. Biol. 2008, 28, 333–343.
  20. Hasimoto, H. The role of the W-chromosome in the sex determination of Bombyx mori. Jpn. J. Genet. 1933, 8, 245–247.
  21. Abe, H.; Fujii, T.; Tanaka, N.; Yokoyama, T.; Kakehashi, H.; Ajimura, M.; Mita, K.; Banno, Y.; Yasukochi, Y.; Oshiki, T.; et al. Identification of the female-determining region of the W chromosome in Bombyx mori. Genetica 2008, 133, 269–282.
  22. Xia, Q.; Zhou, Z.; Lu, C.; Cheng, D.; Dai, F.; Li, B.; Zhao, P.; Zha, X.; Cheng, T.; Chai, C.; et al. A draft sequence for the genome of the domesticated silkworm (Bombyx mori). Science 2004, 306, 1937–1940.
  23. Abe, H.; Mita, K.; Yasukochi, Y.; Oshiki, T.; Shimada, T. Retrotransposable elements on the W chromosome of the silkworm, Bombyx mori. Cytogenet. Genome Res. 2005, 110, 144–151.
  24. Kawaoka, S.; Hayashi, N.; Suzuki, Y.; Abe, H.; Sugano, S.; Tomari, Y.; Shimada, T.; Katsuma, S. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes. RNA 2009, 15, 1258–1264.
  25. Kawaoka, S.; Kadota, K.; Arai, Y.; Suzuki, Y.; Fujii, T.; Abe, H.; Yasukochi, Y.; Mita, K.; Sugano, S.; Shimizu, K.; et al. The silkworm W chromosome is a source of female-enriched piRNAs. Rna 2011, 17, 2144–2151.
  26. Kawaoka, S.; Mitsutake, H.; Kiuchi, T.; Kobayashi, M.; Yoshikawa, M.; Suzuki, Y.; Sugano, S.; Shimada, T.; Kobayashi, J.; Tomari, Y.; et al. A role for transcription from a piRNA cluster in de novo piRNA production. RNA 2012, 18, 265–273.
  27. Hara, K.; Fujii, T.; Suzuki, Y.; Sugano, S.; Shimada, T.; Katsuma, S.; Kawaoka, S. Altered expression of testis-specific genes, piRNAs, and transposons in the silkworm ovary masculinized by a W chromosome mutation. BMC Genom. 2012, 13.
  28. Kawaoka, S.; Arai, Y.; Kadota, K.; Suzuki, Y.; Hara, K.; Sugano, S.; Shimizu, K.; Tomari, Y.; Shimada, T.; Katsuma, S. Zygotic amplification of secondary piRNAs during silkworm embryogenesis. RNA 2011, 17, 1401–1407.
  29. Ishizu, H.; Siomi, H.; Siomi, M.C. Biology of Piwi-interacting RNAs: New insights into biogenesis and function inside and outside of germlines. Genes Dev. 2012, 26, 2361–2373.
  30. Sato, K.; Siomi, M.C. The piRNA pathway in Drosophila ovarian germ and somatic cells. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2020, 96, 32–42.
  31. Sakakibara, K.; Siomi, M.C. The PIWI-Interacting RNA Molecular Pathway: Insights from Cultured Silkworm Germline Cells. BioEssays 2018, 40.
  32. Czech, B.; Munafò, M.; Ciabrelli, F.; Eastwood, E.L.; Fabry, M.H.; Kneuss, E.; Hannon, G.J. PiRNA-guided genome defense: From biogenesis to silencing. Annu. Rev. Genet. 2018, 52, 131–157.
  33. Ozata, D.M.; Gainetdinov, I.; Zoch, A.; O’Carroll, D.; Zamore, P.D. PIWI-interacting RNAs: Small RNAs with big functions. Nat. Rev. Genet. 2019, 20, 89–108.
  34. Ohtani, H.; Iwasaki, Y.W.; Shibuya, A.; Siomi, H.; Siomi, M.C.; Saito, K. DmGTSF1 is necessary for Piwi-piRISC-mediated transcriptional transposon silencing in the Drosophila ovary. Genes Dev. 2013, 27, 1656–1661.
  35. Dönertas, D.; Sienski, G.; Brennecke, J. Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex. Genes Dev. 2013, 27, 1693–1705.
  36. Sienski, G.; Dönertas, D.; Brennecke, J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 2012, 151, 964–980.
  37. Chen, K.; Chen, S.; Xu, J.; Yu, Y.; Liu, Z.; Tan, A.; Huang, Y. Maelstrom regulates spermatogenesis of the silkworm, Bombyx mori. Insect Biochem. Mol. Biol. 2019, 109, 43–51.
  38. Izumi, N.; Shoji, K.; Sakaguchi, Y.; Honda, S.; Kirino, Y.; Suzuki, T.; Katsuma, S.; Tomari, Y. Identification and Functional Analysis of the Pre-piRNA 3′ Trimmer in Silkworms. Cell 2016, 164, 962–973.
  39. Chen, S.; Liu, Y.; Yang, X.; Liu, Z.; Luo, X.; Xu, J.; Huang, Y. Dysfunction of dimorphic sperm impairs male fertility in the silkworm. Cell Discov. 2020, 6.
  40. Krzywinska, E.; Dennison, N.J.; Lycett, G.J.; Krzywinski, J. A maleness gene in the malaria mosquito Anopheles gambiae. Science 2016, 353, 67–69.
  41. Katsuma, S.; Sugano, Y.; Kiuchi, T.; Shimada, T. Two conserved cysteine residues are required for the masculinizing activity of the silkworm Masc protein. J. Biol. Chem. 2015, 290, 26114–26124.
  42. Fukui, T.; Kawamoto, M.; Shoji, K.; Kiuchi, T.; Sugano, S.; Shimada, T.; Suzuki, Y.; Katsuma, S. The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene. PLoS Pathog. 2015, 11, e1005048.
  43. Zhao, Q.; Li, J.; Wen, M.Y.; Wang, H.; Wang, Y.; Wang, K.X.; Wan, Q.X.; Zha, X.F. A novel splice variant of the masculinizing gene masc with piRNA-cleavage-site defect functions in female external genital development in the silkworm, bombyx mori. Biomolecules 2019, 9, 318.
  44. Gempe, T.; Hasselmann, M.; Schiøtt, M.; Hause, G.; Otte, M.; Beye, M. Sex determination in honeybees: Two separate mechanisms induce and maintain the female pathway. PLoS Biol. 2009, 7.
  45. Zhuo, J.C.; Zhang, H.H.; Xie, Y.C.; Li, H.J.; Hu, Q.L.; Zhang, C.X. Identification of a female determinant gene for the sexual determination of a hemipteran insect, the brown planthopper. bioRxiv 2019.
  46. Krzywinska, E.; Ferretti, L.; Li, J.; Li, J.-C.; Chen, C.-H.; Krzywinski, J. femaleless controls sex determination and dosage compensation pathways in females of the Anopheles mosquitoes. Curr. Biol. 2021, 1–8.
  47. Siebel, C.W.; Kanaar, R.; Rio, D.C. Regulation of tissue-specific P-element pre-mRNA splicing requires the RNA-binding protein PSI. Genes Dev. 1994, 8, 1713–1725.
  48. Labourier, E.; Adams, M.D.; Rio, D.C. Modulation of P-element pre-mRNA splicing by a direct interaction between PSI and U1 snRNP 70K protein. Mol. Cell 2001, 8, 363–373.
  49. Adams, M.D.; Tarng, R.S.; Rio, D.C. The alternative splicing factor PSI regulates P-element third intron splicing in vivo. Genes Dev. 1997, 11, 129–138.
  50. Amarasinghe, A.K.; Macdiarmid, R.; Adams, M.D.; Rio, D.C. An in vitro-selected RNA-binding site for the KH domain protein PSI acts as a splicing inhibitor element. RNA 2001, 7, 1239–1253.
  51. Chmiel, N.H.; Rio, D.C.; Doudna, J.A. Distinct contributions of KH domains to substrate binding affinity of Drosophila P-element somatic inhibitor protein. RNA 2006, 12, 283–291.
  52. Ignjatovic, T.; Yang, J.C.; Butler, J.; Neuhaus, D.; Nagai, K. Structural basis of the interaction between P-element somatic inhibitor and U1-70k essential for the alternative splicing of P-element transposase. J. Mol. Biol. 2005, 351, 52–65.
  53. Wang, Y.; Zhao, Q.; Wan, Q.X.; Wang, K.X.; Zha, X.F. P-element somatic inhibitor protein binding a target sequence in dsx pre-mrna conserved in Bombyx mori and Spodoptera litura. Int. J. Mol. Sci. 2019, 20, 2361.
  54. Gopinath, G.; Arunkumar, K.P.; Mita, K.; Nagaraju, J. Role of Bmznf-2, a Bombyx mori CCCH zinc finger gene, in masculinisation and differential splicing of Bmtra-2. Insect Biochem. Mol. Biol. 2016, 75, 32–44.
  55. Guo, J.; Tang, H.W.; Li, J.; Perrimon, N.; Yan, D. Xio is a component of the Drosophila sex determination pathway and RNA N6-methyladenosine methyltransferase complex. Proc. Natl. Acad. Sci. USA 2018, 115, 3674–3679.
  56. Lence, T.; Akhtar, J.; Bayer, M.; Schmid, K.; Spindler, L.; Ho, C.H.; Kreim, N.; Andrade-Navarro, M.A.; Poeck, B.; Helm, M.; et al. M6A modulates neuronal functions and sex determination in Drosophila. Nature 2016, 540, 242–247.
  57. Kan, L.; Grozhik, A.V.; Vedanayagam, J.; Patil, D.P.; Pang, N.; Lim, K.S.; Huang, Y.C.; Joseph, B.; Lin, C.J.; Despic, V.; et al. The m6A pathway facilitates sex determination in Drosophila. Nat. Commun. 2017, 8, 1–16.
  58. Haussmann, I.U.; Bodi, Z.; Sanchez-Moran, E.; Mongan, N.P.; Archer, N.; Fray, R.G.; Soller, M. M6 A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 2016, 540, 301–304.
  59. Garrett-Engele, C.M.; Siegal, M.L.; Manoli, D.S.; Williams, B.C.; Li, H.; Baker, B.S. intersex, a gene required for female sexual development in Drosophila, is expressed in both sexes and functions together with doublesex to regulate terminal differentiation. Development 2002, 129, 4661–4675.
  60. Zheng, Z.Z.; Sun, X.; Zhang, B.; Pu, J.; Jiang, Z.Y.; Li, M.; Fan, Y.J.; Xu, Y.Z. Alternative splicing regulation of doublesex gene by RNA-binding proteins in the silkworm Bombyx mori. RNA Biol. 2019, 16, 809–820.
  61. Xu, J.; Yu, Y.; Chen, K.; Huang, Y. Intersex regulates female external genital and imaginal disc development in the silkworm. Insect Biochem. Mol. Biol. 2019, 108, 1–8.
  62. Yuzawa, T.; Matsuoka, M.; Sumitani, M.; Aoki, F.; Sezutsu, H.; Suzuki, M.G. Transgenic and knockout analyses of Masculinizer and doublesex illuminated the unique functions of doublesex in germ cell sexual development of the silkworm, Bombyx mori. BMC Dev. Biol. 2020, 20, 1–15.
  63. Suzuki, M.G.; Funaguma, S.; Kanda, T.; Tamura, T.; Shimada, T. Role of the male BmDSX protein in the sexual differentiation of Bombyx mori. Evol. Dev. 2005, 7, 58–68.
  64. Xu, J.; Zhan, S.; Chen, S.; Zeng, B.; Li, Z.; James, A.A.; Tan, A.; Huang, Y. Sexually dimorphic traits in the silkworm, Bombyx mori, are regulated by doublesex. Insect Biochem. Mol. Biol. 2017, 80, 42–51.
  65. Bopp, D.; Saccone, G.; Beye, M. Sex determination in insects: Variations on a common theme. Sex. Dev. 2014, 8, 20–28.
  66. Pane, A.; Salvemini, M.; Delli Bovi, P.; Polito, C.; Saccone, G. The transformer gene in Ceratitis capitata provides a genetic basis for selecting and remembering the sexual fate. Development 2002, 129, 3715–3725.
  67. Concha, C.; Scott, M.J. Sexual development in Lucilia cuprina (Diptera, Calliphoridae) is controlled by the transformer gene. Genetics 2009, 182, 785–798.
  68. Liu, G.; Wu, Q.; Li, J.; Zhang, G.; Wan, F. RNAi-mediated knock-down of transformer and transformer 2 to generate male-only progeny in the oriental fruit fly, Bactrocera dorsalis (Hendel). PLoS ONE 2015, 10, e0128892.
  69. Li, F.; Vensko, S.P.; Belikoff, E.J.; Scott, M.J. Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata. PLoS ONE 2013, 8, e56303.
  70. Kyrou, K.; Hammond, A.M.; Galizi, R.; Kranjc, N.; Burt, A.; Beaghton, A.K.; Nolan, T.; Crisanti, A. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat. Biotechnol. 2018, 36, 1062–1071.
  71. Simoni, A.; Hammond, A.M.; Beaghton, A.K.; Galizi, R.; Taxiarchi, C.; Kyrou, K.; Meacci, D.; Gribble, M.; Morselli, G.; Burt, A.; et al. A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae. Nat. Biotechnol. 2020, 38, 1054–1060.
  72. Tan, A.; Fu, G.; Jin, L.; Guo, Q.; Li, Z.; Niu, B.; Meng, Z.; Morrison, N.I.; Alphey, L.; Huang, Y. Transgene-based, female-specific lethality system for genetic sexing of the silkworm, Bombyx mori. Proc. Natl. Acad. Sci. USA 2013, 110, 6766–6770.
  73. Xu, J.; Wang, Y.; Li, Z.; Ling, L.; Zeng, B.; James, A.A.; Tan, A.; Huang, Y. Transcription activator-like effector nuclease (TALEN)-mediated female-specific sterility in the silkworm, Bombyx mori. Insect Mol. Biol. 2014, 23, 800–807.
  74. Suzuki, M.G.; Ohbayashi, F.; Mita, K.; Shimada, T. The mechanism of sex-specific splicing at the doublesex gene is different between Drosophila melanogaster and Bombyx mori. Insect Biochem. Mol. Biol. 2001, 31, 1201–1211.
  75. Suzuki, M.G.; Funaguma, S.; Kanda, T.; Tamura, T.; Shimada, T. Analysis of the biological functions of a doublesex homologue in Bombyx mori. Dev. Genes Evol. 2003, 213, 345–354.
  76. Chen, X.; Cao, Y.; Zhan, S.; Tan, A.; Palli, S.R.; Huang, Y. Disruption of sex-specific doublesex exons results in male- and female-specific defects in the black cutworm, Agrotis ipsilon. Pest Manag. Sci. 2019, 75, 1697–1706.
  77. Li, X.; Liu, Q.; Liu, H.; Bi, H.; Wang, Y.; Chen, X.; Wu, N.; Xu, J.; Zhang, Z.; Huang, Y.; et al. Mutation of doublesex in Hyphantria cunea results in sex-specific sterility. Pest Manag. Sci. 2020, 76, 1673–1682.
  78. Wang, Y.; Chen, X.; Liu, Z.; Xu, J.; Li, X.; Bi, H.; Andongma, A.A.; Niu, C.; Huang, Y. Mutation of doublesex induces sex-specific sterility of the diamondback moth Plutella xylostella. Insect Biochem. Mol. Biol. 2019, 112, 103180.
  79. Billeter, J.C.; Rideout, E.J.; Dornan, A.J.; Goodwin, S.F. Control of Male Sexual Behavior in Drosophila by the Sex Determination Pathway. Curr. Biol. 2006, 16, 766–776.
  80. Xu, J.; Liu, W.; Yang, D.; Chen, S.; Chen, K.; Liu, Z.; Yang, X.; Meng, J.; Zhu, G.; Dong, S.; et al. Regulation of olfactory-based sex behaviors in the silkworm by genes in the sexdetermination cascade. PLoS Genet. 2020, 16, e1008622.
  81. Luo, S.D.; Shi, G.W.; Baker, B.S. Direct targets of the D. melanogaster DSXF protein and the evolution of sexual development. Development 2011, 138, 2761–2771.
  82. Clough, E.; Jimenez, E.; Kim, Y.A.; Whitworth, C.; Neville, M.C.; Hempel, L.U.; Pavlou, H.J.; Chen, Z.X.; Sturgill, D.; Dale, R.K.; et al. Sex- and tissue-specific functions of drosophila doublesex transcription factor target genes. Dev. Cell 2014, 31, 761–773.
  83. Baral, S.; Arumugam, G.; Deshmukh, R.; Kunte, K. Genetic architecture and sex-specific selection govern modular, male-biased evolution of doublesex. Sci. Adv. 2019, 5, 1–9.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Genetics & Heredity
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Xu Yang
View Times: 938
Revisions: 2 times (View History)
Update Date: 19 May 2021
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback