Sex determination caused by failure of X-chromosome dosage compensation in Drosophila germline

Research Project

Project/Area Number	18K14739
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 44040:Morphology and anatomical structure-related
Research Institution	University of Tsukuba
Principal Investigator	Ryoma Ota 筑波大学, 生存ダイナミクス研究センター, 研究員 (00647969)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Discontinued (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	生殖系列 / 性決定 / 遺伝子量補償 / ショウジョウバエ / X染色体 / 始原生殖細胞
Outline of Final Research Achievements	This study aims to clarify the cell-autonomous mechanism of sex determination in Drosophila germline. We have previously found that dosage compensation equalizing X-linked gene expression between the sexes is absent in primordial germ cells (PGCs). Here, we show that hyperactivation of X-linked genes is induced in XY (male) PGCs by overexpression of the essential components of the MSL complex is responsible for dosage compensation in Drosophila. Furthermore, we show a possibility that hyperactivation of X-linked genes induces feminization in XY PGCs. These findings strongly suggest that cell-autonomous sex determination in the germline is resulted from the biased expression of X-linked genes caused by absence of dosage compensation.
Academic Significance and Societal Importance of the Research Achievements	本研究から、未だあらゆる種で十分に明らかになっていない生殖系列自律的な性決定機構に関する重要な知見が得られた。生殖系列自律的な性決定機構は、ショウジョウバエのみならず、ヒトやマウス、メダカなど種を超えて存在することが明らかになりつつある。したがって、本研究の成果は、動物に普遍的な生殖系列の性決定メカニズムを理解するうえで重要な基盤となる。また、本研究で得られた成果は、体細胞系列と生殖系列の性の不一致により起こる不妊の原因究明のための重要な基盤にもなると考えられる。