Educational Activities

Graduate school: Insect development and physiology
Undergraduate school: Insect engineering, Exercise for Applied Biological Experiments (Faculty of Agriculture)

Research Activities

We are interested in sexual differentiation because it is an important theme in the field of development. The sex of insects is determined on a cell-by-cell basis. In other words, sex determination in insect cells is not influenced by the surrounding environment. Therefore, we believe that insect cells are a good model system for understanding sex determination. Since sex determination occurs at early embryonic stage, we set out to establish insect cell lines from male and female embryos. For this purpose, we used embryos of the silkworm strain 'Sex-limited black egg' because this strain allows us to identify the sex of embryos based on the color of the egg shells. We have found that a doublesex homolog, Bmdsx, plays an essential role in silkworm sexual development (2, 3). Bmdsx RNA is alternatively spliced in males and females, and as a result, males have the male-specific BmDSX protein and females have the female-specific BmDSX protein. Therefore, we can conclude that regulation of the sex-specific splicing of Bmdsx RNA is very important for sex determination.To explore how the alternative splicing of Bmdsx specifically regulates sex, we used our male and female cell lines to develop an in vivo splicing assay system. As a result, we successfully identified a cis-acting element CE1 and a trans-acting factor BmPSI that regulate sex-specific splicing of Bmdsx RNA (1).Now we are trying to identify factors that interact with BmPSI to elucidate how BmPSI represses inclusion of female-specific Bmdsx exons in a male-specific manner.We are also trying to develop an efficient gene-targeting technique in the silkworm.

Literature

(1) Kaneda T, Matsuda-Imai N, Kosako H, Shoji K, Suzuki MG, Suzuki Y, Kiuchi T, Katsuma S. (2025) The Masc-PSI complex directly induces male-type doublesex splicing in silkworms. Commun Biol. 8:927.
(2) Yamamoto F, Yokoyama T, Su Y, Suzuki MG*. (2024) Transcriptomic Evidence for Cell-Autonomous Sex Differentiation of the Gynandromorphic Fat Body in the Silkworm, Bombyx mori. J Dev Biol. 12:31.
(3) Moronuki Y, Kasahara R, Naka H, Suzuki MG*. (2024) Identification and functional analysis of sex-determining genes in the spongy moth, Lymantria dispar (lepidoptera: Erebidae). Insect Biochem Mol Biol. 177:104219.
(4) Hattori M, Takase D, Aoki F, Suzuki MG*. (2024) Role of doublesex-dependent phosphodiesterase 1c expression in gustatory receptor neurons in male courtship behavior of Drosophila melanogaster. Int J Neurobiol. 6:1-8.
(5) Funaya S, Takahashi Y, Suzuki MG, Suzuki Y, Aoki F. (2024) H3.1/3.2 regulate the initial progression of the gene expression program. Nucleic Acids Res. 52:6158-6170.
(6) Funaya S, Wang Y, Suzuki MG, Ikawa M, Aoki F. (2023) Involvement of linker histone variant H1a in the regulation of early preimplantation development in mice. J Reprod Dev. 69:178-182.
(7) Suzuki Y, Yamada T, Suzuki MG*. (2023) In vitro comparison of sex-specific splicing efficiencies of fem pre-mRNA under monoallelic and heteroallelic conditions of csd, a master sex-determining gene in the honeybee. J Dev Biol. 11:10.
(8) Wang Y, Oda S, Suzuki MG, Mitani H, Aoki F. (2022) Cell cycle-dependent radiosensitivity in mouse zygotes. DNA Repair (Amst). 117:103370.
(9) Funaya S, Kawabata Y, Sugie K, Abe KI, Suzuki Y, Suzuki MG, Aoki F. (2022) Involvement of the linker histone H1Foo in the regulation of oogenesis. Reproduction. 164:19-29.
(10) Mine S, Sumitani M, Aoki F, Hatakeyama M, Suzuki MG*. (2021) Effects of functional depletion of doublesex on male development in the Sawfly, Athalia rosae. Insects. 12:849.
(11) Kawamura M, Funaya S, Sugie K, Suzuki MG, Aoki F. (2021) Asymmetrical deposition and modification of histone H3 variants are essential for zygote development. Life Sci Alliance. 4:e202101102.
(12) Kasahara R, Yuzawa T, Fujii T, Aoki F, Suzuki MG*. (2020) dmrt11E ortholog is a crucial factor for oogenesis of the domesticated silkworm, Bombyx mori. Insect Biochem Mol Biol. 129:103157.
(13) Sugie K, Funaya S, Kawamura M, Nakamura T, Suzuki MG, Aoki F*. (2020) Expression of Dux family genes in early preimplantation embryos. Sci Rep. 10:1-10.
(14) Yuzawa T, Matsuoka M, Sumitani M, Aoki F, Sezutsu H, Suzuki MG*. (2020) 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. 20:1-15.
(15) Matsushima D, Kasahara R, Matsuno K, Aoki F, Suzuki MG*. (2019) Involvement of ecdysone signaling in the expression of the doublesex gene during embryonic development in the silkworm, Bombyx mori. Sex Dev. 13:151-163.
(16) Abe KI, Funaya S, Tsukioka D, Kawamura M, Suzuki Y, Suzuki MG, Schultz RM, Aoki F*. (2018) Minor zygotic gene activation is essential for mouse preimplantation development. Proc Natl Acad Sci U S A. 115:E6780-E6788.
(17) Funaya S, Ooga M, Suzuki MG, Aoki F*. (2018) Linker histone H1FOO regulates the chromatin structure in mouse zygotes. FEBS Lett. 592:2414-2424.
(18) Takase D, Suzuki MG*. (2018) Analysis of sex-specific regulation of the dunce gene in the Drosophila melanogaster central nervous system. Cytologia, 83:345-346.
(19) Kasahara R, Fugaku A, Suzuki MG*. (2018) Deficiency in dmrt99B ortholog causes behavioral abnormalities in the silkworm, Bombyx mori. Appl Entomol Zool. 53:381-393.
(20) Tanaka A, Aoki F, Suzuki MG*. (2018) Conserved domains in Transformer protein act complementary to regulate sex-specific splicing of its own pre-mRNA. Sex Dev. 12:189-190.
(21) Ooga M, Funaya S, Hashioka Y, Fujii W, Naito K, Suzuki MG, and Aoki F*. (2018) Chd9 mediates highly loosened chromatin structure in growing mouse oocytes. Biochem Biophys Res Commun. 500:583-588.
(22) Mine S, Sumitani M, Aoki F, Hatakeyama M, and Suzuki MG*. (2017) Identification and functional characterization of the sex-determining gene doublesex in the sawfly, Athalia rosae. Appl Entomol Zool. 52:497-509.
(23) Wagamitsu S, Takase D, Aoki F, and Suzuki MG*. (2017) Identification of the Doublesex protein binding sites that activate expression of lozenge in the female genital disc in Drosophila melanogaster. Mech Dev. 143:26-31.
(24) Sakai H, Sumitani M, Chikami Y, Yahata, K. Uchino K, Kiuchi T, Katsuma S, Aoki F, Sezutsu H, Suzuki MG*. (2016) Transgenic expression of the piRNA-resistant Masclinizer gene induces female-specific lethality and partial female-to-male sex reversal in the silkworm, Bombyx mori. PLoS Genet. 12, 2016, e1006203.
(25) Sakai H, Kirino Y, Katsuma S, Aoki F, Suzuki MG*. (2016). Morphological and histological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori. Journal of Insect Biotechnology and Sericology. 85:15-20.
(26) Ooga M, Fulka H, Hashimoto S, Suzuki MG, Aoki F*. (2016). Analysis of chromatin structure in mouse preimplantation embryos by fluorescent recovery after photobleaching. Epigenetics. 11:85-94.
(27) Yamamoto R, Abe K, Suzuki Y, Suzuki MG, Aoki F*. (2016). Characterization of gene expression in mouse embryos at the 1-cell stage. J Reprod Dev. 62:87-92.
(28) Abe K, Yamamoto R, Franke V, Cao M, Suzuki Y, Suzuki MG, Vlahovicek K, Svoboda P, Schultz RM, Aoki F*. (2015). The first murine zygotic transcription is promiscuous and uncoupled from splicing and 3' processing. EMBO J. 34:1523-1537.
(29) Suzuki MG*, Tochigi M, Sakaguchi H, Aoki F, Miyamoto N. (2015). Identification of a transformer homolog in the acorn worm, Saccoglossus kowalevskii, and analysis of its activity in insect cells. Dev Genes Evol. 225:161-169.
(30) Sakai H, Sakaguchi H, Aoki F, Suzuki MG*. (2015). Functional analysis of sex-determination genes by gene silencing with LNA-DNA gapmers in the silkworm, Bombyx mori. Mech Dev. 137:45-52.
(31) Ooga M, Suzuki MG, Aoki F*. (2015). Involvement of histone H2B monoubiquitination in the regulation of mouse preimplantation development. J Reprod Dev. 61:179-184.
(32) Suzuki MG*, Kobayashi S, Aoki F. (2014). Male-specific splicing of the silkworm Imp gene is maintained by an autoregulatory mechanism. Mech. Dev. 131: 47-56.
(33) Sakai H, Aoki F, Suzuki MG*. (2014). Identification of the key stages for sex determination in the silkworm, Bombyx mori. Dev. Genes. Evol. 224: 119-123.
(34) Hamamoto G, Suzuki T, Suzuki MG, Aoki F*. (2014). Regulation of transketolase like 1 gene expression in the murine one-cell stage embryos. PLoS One. 9: e82087.
(35) Yukawa M, Akiyama T, Franke V, Mise N, Isagawa T, Suzuki Y, Suzuki MG, Vlahovicek K, Abe K, Aburatani H, Aoki F*. (2014). Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells. PLoS One. 9: e92689.
(36) Suzuki MG*, Ito H, Aoki F. (2014). Effects of RNAi-mediated knockdown of histone methyltransferases on the sex-specific mRNA expression of Imp in the silkworm Bombyx mori. Int. J. Mol. Sci., 15: 6772-6796.
(37) Kiuchi T, Koga H, Kawamoto M, Shoji K, Sakai H, Arai Y, Ishihara G, Kawaoka S, Sugano S, Shimada T, Suzuki Y, Suzuki MG, Katsuma S*. (2014). A single female-specific piRNA is the primary determiner of sex in the silkworm. Nature, 509:633-636.
(38) Suetsugu Y, Futahashi R, Kanamori H, Kadono-Okuda K, Sasanuma S, Narukawa J, Ajimura M, Jouraku A, Namiki N, Shimomura M, Sezutsu H, Osanai-Futahashi M, Suzuki MG, 他22名, Mita K.* (2013). Large scale full-length cDNA sequencing reveals a unique genomic landscape in a lepidopteran model insect, Bombyx mori. G3 (Bethesda). 3: 1481-1492.
(39) Sakaguchi H, Suzuki MG*. (2013). Drosophila melanogaster larvae control amylase secretion according to the hardness of food. Frontiers in Physiology. 4: 200.
(40) Sakai H, Yokoyama T, Abe H, Fujii T, Suzuki MG*. (2013). Appearance of differentiated cells derived from polar body nuclei in the silkworm, Bombyx mori. Frontiers in Physiology. 4: 235.
(41) Ooga M, Suzuki MG, Aoki F.* (2013). Involvement of DOT1L in the remodeling of heterochromatin configuration during early preimplantation development in mice. Biology of Reproduction, 89: 145.
(42) Fujii T, Suzuki MG, Katsuma S, Ito K, Rong Y, Matsumoto S, Ando T, Ishikawa Y.* (2013). Discovery of a disused desaturase gene from the pheromone gland of the moth Ascotis selenaria, which secretes an epoxyalkenyl sex pheromone. Biochem. Biophys. Res. Commun., 441: 849-855.
(43) Kawamura M, Akiyama T, Tsukamoto S, Suzuki MG, Aoki F.* (2012). The expression and nuclear deposition of histone H3.1 in murine oocytes and preimplantation embryos. Journal of Reproduction and Development., 58: 557-562.
(44) Suzuki MG*, Suzuki K, Aoki F, Ajimura M. (2012). Effect of RNAi-mediated knockdown for Bombyx mori transformer-2 gene on the sex-specific splicing of Bmdsx pre-mRNA. International Journal of Developmental Biology, 56: 693-699.
(45) Nashun B, Akiyama T, Suzuki MG, Aoki F.* (2011). Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos. Epigenetics, 6:1489-1497.
(46) Inoue A, Ogushi S, Saitou M, Suzuki MG, Aoki F.* (2011). Involvement of mouse nucleoplasmin 2 in the decondensation of sperm chromatin after fertilization. Biol Reprod. 85:70-77.
(47) Suzuki MG*, Imanishi S, Dohmae N, Asanuma M, Matsumoto S. (2010). Identification of a male-specific RNA binding protein that regulates sex-specific splicing of Bmdsx by increasing RNA binding activity of BmPSI. Mol Cell Biol. 30:5776-5786.
(48) Abe K., Inoue A., Suzuki MG, Aoki F.* (2010) Global gene silencing is caused by the dissociation of RNA polymerase II from DNA in mouse oocytes. J. Reprod. Dev. 56:502-507.
(49) Suzuki MG*, Imanishi S, Dohmae N, Nishimura T, Shimada T, Matsumoto S. (2008) 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. 28:333-343.

Other Activities

The Japanese Society of Sericultural Science (JSSS)
The Molecular Biology Society of Japan (MBSJ)
The Japanese Society of Applied Entomology & Zoology (JSAEZ)

Future Plan

On the basis of the findings for fruit flies and the silkworm, we will elucidate the sex-determining mechanisms of other insects. We also want to verify the unique characteristics of and the similarities between insects and vertebrates. We will attempt to investigate developmental mechanisms of germ cells in insects as closely related to sexual differentiation. In addition, we will focus on the functional characteristics of insects in an attempt to develop new biological resources.

Messages to Students

Insects are the most thriving creatures on Earth. Therefore, insects may have many excellent values as biological resources. In addition, insects may provide clues on how to overcome hurdles in life. I hope that you will master the skills necessary for scientists and learn some skills for everyday life through studying insects.

URL

http://webpark1599.sakura.ne.jp/seigyo/