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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Development (Cambridge, England)  

Gametogenesis is the process through which germ cells differentiate into sexually dimorphic gametes, eggs and sperm. In the teleost fish medaka (Oryzias latipes), a germ cell-intrinsic sex determinant, foxl3, triggers germline feminization by activating two genetic pathways that regulate folliculogenesis and meiosis. Here, we identified a pathway involving a dome-shaped microtubule structure that may be the basis of oocyte polarity. This structure was first established in primordial germ cells in both sexes, but was maintained only during oogenesis and was destabilized in differentiating spermatogonia under the influence of Sertoli cells expressing dmrt1. Although foxl3 was dispensable for this pathway, dazl was involved in the persistence of the microtubule dome at the time of gonocyte development. In addition, disruption of the microtubule dome caused dispersal of bucky ball RNA, suggesting the structure may be prerequisite for the Balbiani body. Collectively, the present findings provide mechanistic insight into the establishment of sex-specific polarity through the formation of a microtubule structure in germ cells, as well as clarifying the genetic pathways implementing oocyte-specific characteristics.

DOI： 10.1242/dev.201840

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Cell and Developmental Biology  

Gametogenesis, the production of eggs and sperm, is a fundamental process in sexually reproducing animals. Following gametogenesis commitment and sexual fate decision, germ cells undergo several developmental processes to halve their genomic size and acquire sex-specific characteristics of gametes, including cellular size, motility, and cell polarity. However, it remains unclear how different gametogenesis processes are initially integrated. With the advantages of the teleost fish medaka (Oryzias latipes), in which germline stem cells continuously produce eggs and sperm in mature gonads and a sexual switch gene in germ cells is identified, we found that distinct pathways initiate gametogenesis cooperatively after commitment to gametogenesis. This evokes the concept of functional modules, in which functionally interlocked genes are grouped to yield distinct gamete characteristics. The various combinations of modules may allow us to explain the evolution of diverse reproductive systems, such as parthenogenesis and hermaphroditism.

DOI： 10.3389/fcell.2022.914570

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1073/pnas.1918556117/-/DCSupplemental

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Developmental Biology  

Germline sex determination is an essential process for the production of sexually dimorphic gametes. In medaka, Forkhead box L3 (foxl3) was previously identified as a germ cell-intrinsic regulator of sex determination that suppresses the initiation of spermatogenesis in female germ cells. To reveal the molecular mechanism of germline sex determination by foxl3, we conducted the following four analyses: Comparison of transcriptomes between wild-type and foxl3-mutant germ cells; epistatic analysis; identification of the FOXL3-binding motif; and ChIP-qPCR assay using a FOXL3-monoclonal antibody. We identified two candidate genes acting downstream of foxl3: Rec8a and fbxo47. It has been known that Rec8 regulates sister chromatid cohesion and Fbxo47 acts as a ubiquitin E3 ligase. These functions have not been, however, associated with sexual differentiation in germ cells. Our results uncover novel components acting downstream of foxl3, providing insights into the mechanism of germline sex determination.

DOI： 10.1016/j.ydbio.2018.10.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Reproduction and Development  

In vertebrates, there is accumulating evidence that environmental factors as triggers for sex determination and genetic sex determination are not two opposing alternatives but that a continuum of mechanisms bridge those extremes. One prominent example is the model fish species Oryzias latipes which has a stable XX/XY genetic sex determination system, but still responds to environmental cues, where high temperatures lead to female-to-male sex reversal. However, the mechanisms behind are still unknown. We show that high temperatures increase primordial germ cells (PGC) numbers before they reach the genital ridge, which, in turn, regulates the germ cell proliferation. Complete ablation of PGCs led to XX males with germ cell less testis, whereas experimentally increased PGC numbers did not reverse XY genotypes to female. For the underlying molecular mechanism, we provide support for the explanation that activation of the dmrt1a gene by cortisol during early development of XX embryos enables this autosomal gene to take over the role of the male determining Y-chromosomal dmrt1bY.

DOI： 10.1002/mrd.23177

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総ページ数：4   担当ページ：pp.20-23   記述言語：日本語

細胞レベルでの性的アイデンティティーは、さまざまな環境要因によって揺らぎ、ときには全身の性にも影響をおよぼす。しかしながら、環境因子が細胞の性を変える分子基盤の全容は解明されていない。魚類の中には、環境要因による性転換を生殖戦略として用い る種が多数存在するほか、遺伝的に性が決まる魚であっても環境要因によって性転換が引き起こされることがある。たとえばメダカの性は遺伝的に決まるが、高温や飢餓などのストレスに晒されるとメスからオスへの性転換が引き起こされる。環境の変化に応じて細 胞の性が揺らぐ根底には、性的な可塑性を補償する分子機構が存在しているはずである。本稿では、メダカを用いた筆者らの研究から、性の揺らぎをもたらす環境要因、特に飢餓条件における脂質量の変化が生殖腺体細胞の性を変えるメカニズムについて紹介した。また、生殖腺の性に応じて生殖細胞が柔軟に性を変える分子基盤についても紹介した。

開催年月日： 2024年3月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：オンライン   国名：日本国  

開催年月日： 2024年3月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：東京大学 弥生キャンパス   国名：日本国  

開催年月日： 2023年12月

記述言語：英語   会議種別：口頭発表（招待・特別）  

開催地：国立遺伝学研究所   国名：日本国  

開催年月日： 2023年12月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

国名：日本国  

開催年月日： 2023年4月

記述言語：英語   会議種別：ポスター発表  

開催地：Kailua-Kona, Hawaii   国名：アメリカ合衆国  

執筆者：本人以外 

執筆者：本人以外 

執筆者：本人以外 

執筆者：本人以外 

執筆者：本人以外 

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