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: 10389978
• 负责人: Mark B Van Doren
• 金额: $ 1.23万
• 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/10389978
• 关键词: Animals; Chromosomes; Cladocera; Development; Developmental Process; Drosophila genus; Environment; Exhibits; Female; Genes; Genomics; Germ Cells; Goals; Gonadal Disorders; Gonadal structure; Human; Life; Mammals; Mus; Nature; Organism; Ovary; Patients; Process; Regulation; System; Testis; daughter cell; fly; germline stem cells; gonad development; interest; male; man; reproductive system disorder; sex; sexual dimorphism; stem cell niche; stem cell population; stem cells; 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.

项目概要 Doublesex 调节的性腺干细胞系统的性别特异性发育 果蝇 Doublesex (Dsx) 的同源物，即 Dsx-Mab3 相关转录因子 (DMRT)，现已成为 已知可以控制整个动物界的性腺性别二态性，从涡虫和水蚤到 蠕虫、苍蝇、老鼠和人。染色体 9p22 区域缺失的男性患者，包括 DMRT 1-3，表现出生殖器和性腺（包括卵睾）疾病，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 性二态性，一个关键问题是这些转录因子如何调节这一过程以及什么 他们的目标基因是什么？在这里，我们建议使用基因组学和发育学研究这些问题 接近。特别值得关注的是男性和女性的发育过程。 女性干细胞系统。在哺乳动物中，这个过程是高度二态性的，因为睾丸具有干细胞系统 但卵巢则不然。然而，在许多动物中，卵巢和睾丸都具有干细胞系统 两性都需要产生大量配子才能延长生命。这些干细胞系统 两性之间也存在高度二态性。此外，许多生物体的性腺都具有成体干细胞 (SSC) 群体以及生殖系干细胞 (GSC)，并且 SSC 产生分化的子细胞 培育正在发育的配子的细胞。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 SSC 以及控制的生态位环境 他们。