Regulation of Sex-Specific Gonad Stem Cell Niche Development by Doublesex

Doublesex 对性别特异性性腺干细胞生态位发育的调节

• 批准号: 10212407
• 负责人: Mark B Van Doren
• 金额: $ 36.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212407
• 关键词: Animals; Attention; Behavior; Cells; Characteristics; Chromosome Deletion; Chromosomes; Cladocera; Collaborations; Cyst; Data; Defect; Development; Developmental Process; Drosophila genus; Ecdysone; Embryo; Environment; Epithelial; Exhibits; Family; Female; Feminization; Genes; Genomics; Germ Cells; Goals; Gonadal Disorders; Gonadal structure; Hormones; Human; Invertebrates; Lead; Life; Maintenance; Mammals; Mus; Nature; Organism; Ovary; Patients; Play; Population; Process; Production; Proliferating; Regulation; Role; Sexual Development; Signal Transduction; Somatic Cell; Spermatogenesis; Stem Cell Development; Supporting Cell; System; Systems Development; Testing; Testis; Thinking; Time; Tissues; Vertebrates; Work; adult stem cell; cell type; daughter cell; ecdysone receptor; fly; germline stem cells; gonad development; hormonal signals; insight; interest; male; man; mutant; reproductive system disorder; response; sex; sex determination; sexual dimorphism; sexual identity; single-cell RNA sequencing; stem cell niche; stem cell population; stem cells; steroid hormone; transcription factor

Project Summary Sex-specific development of the gonad stem cell systems regulated by Doublesex Homologs of Drosophila Doublesex (Dsx), the Dsx-Mab3 Related Transcription Factors (DMRTs), are now known to control gonad sexual dimorphism across the animal kingdom, from planaria and water fleas, to worms, flies, mice and man. Male patients with deletions in the region of chromosome 9p22, and including DMRT's 1-3, exhibit disorders of the genitalia and gonads including ovotestes, indicating that DMRTs are essential for male gonad development in humans. Given the universal nature of DMRT involvement in gonad sexual dimorphism, a key question becomes how do these transcription factors regulate this process and what are their target genes? Here we propose to study these questions using both genomic and developmental approaches. In particular, a developmental process of high interest is in the development of the male and female stem cell systems. In mammals, this process is highly dimorphic as the testis has a stem cell system but the ovary does not. However, in many animals, both the ovary and the testis have stem cell system since both sexes need to produce large numbers of gametes for an extended period of life. These stem cell systems are also highly dimorphic between the sexes. Further, gonads of many organisms have a somatic stem cell (SSC) population in addition to the germline stem cells (GSCs), and the SSCs produce differentiating daughter cells that nurture the developing gametes. Here, we propose to study how Dsx acts to control two key aspects of the male and female stem cell systems, the male and female SSCs and the niche environments that control them.

项目摘要 双性生殖调控的性腺干细胞系统的性别特异性发育 双性果蝇的同源物，双性果蝇Mab3相关转录因子(DMRT)，现在是 已知控制整个动物界的性腺二型性，从浮萍和水蚤，到 蠕虫、苍蝇、老鼠和人。染色体9p22区域缺失的男性患者，包括 DMRT的1-3个，表现为生殖器和性腺包括卵巢的紊乱，表明DMRT是 对人类男性性腺发育至关重要。鉴于DMRT参与性腺的普遍性 性二型，一个关键的问题是这些转录因子是如何调节这一过程的，以及 他们的目标基因是什么？在这里，我们建议用基因组和发育来研究这些问题。 接近了。特别是，一个令人高度感兴趣的发展过程是在男性和 女性干细胞系统。在哺乳动物中，这一过程是高度二态的，因为睾丸有一个干细胞系统。 但卵巢不会。然而，在许多动物中，卵巢和睾丸都有干细胞系统，因为 为了延长生命周期，两性都需要产生大量的配子。这些干细胞系统 在两性之间也是高度二态的。此外，许多生物的性腺都有体细胞干细胞。 生殖系干细胞(GSCs)以外的(SSC)群体，SSCs产生分化的子代 滋养发育中配子的细胞。在这里，我们建议研究dsx如何控制两个关键方面 男性和女性干细胞系统、男性和女性SSCs以及控制 他们。