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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

基本信息

批准号：
10629405
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
项目类别：
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/10629405
关键词：
Animals Attention Behavior Cell Proliferation Cells Characteristics Chromosome Deletion Chromosomes Cladocera Collaborations Cyst Data Decision Making Defect Development Developmental Process Drosophila genus Ecdysone Embryo Environment Epithelium Exhibits Family Female Feminization Genes Genomics Germ Cells Goals Gonadal Disorders Gonadal structure Homologous Gene Hormones Human Invertebrates Lead Life Maintenance Mammals Mus Nature Organism Ovary Patients Play Population Process Production Regulation Role Sexual Development Signal Transduction Somatic Cell Spermatogenesis Stem Cell Development Supporting Cell System 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

项目摘要

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 Doubloex调控的性腺干细胞系统的性别特异性发育 Dsx-Mab 3相关转录因子（Dsx-Mab 3 Related Transcription Factors，DMRTs）是果蝇Doublemex（Dsx）的同源物，已知控制性腺两性异形的动物王国，从涡虫和水蚤，蠕虫、苍蝇、小鼠和人。染色体9 p22区域缺失的男性患者，包括 DMRT的1-3，表现出生殖器和性腺包括卵睾丸的疾病，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，一个关键的问题是这些转录因子如何调节这一过程，是它们的目标基因吗在这里，我们建议使用基因组和发育两种方法来研究这些问题。接近。特别地，高度感兴趣的发育过程是雄性的发育，女性干细胞系统在哺乳动物中，这一过程是高度二态性的，因为睾丸具有干细胞系统但卵巢没有然而，在许多动物中，卵巢和睾丸都有干细胞系统，两性都需要产生大量的配子以延长寿命。这些干细胞系统在两性之间也有很高的二态性。此外，许多生物的性腺都有体干细胞 (SSC)除了生殖系干细胞（GSC）外，SSCs还产生分化的子代细胞。滋养配子发育的细胞。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和控制的生态位环境他们