Molecular mechanisms of sex-specific differentiation

性别特异性分化的分子机制

• 批准号: 10678628
• 负责人: Miranda Wilson
• 金额: $ 4.75万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-04 至 2026-05-03
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678628
• 关键词: Adult; Affect; Affinity Chromatography; Binding Sites; Biological Assay; Characteristics; Chromosome 4; Chromosomes; Cloning; Complex; Cytosine; DNA; DNA Methylation; Data; Dedications; Development; Developmental Biology; Drosophila genus; Embryonic Development; Environmental Risk Factor; Etiology; Event; FRAP1 gene; Failure; Female; Fertility; Fertility Disorders; Fostering; Gene Expression; Generations; Genes; Genetic; Genomics; Germ cell tumor; Gonadal Dysgenesis; Gonadal structure; Health; Hormonal; Human; Impairment; Individual; Infertility; Laboratories; Life; Link; Maintenance; Malignant Neoplasms; Mammals; Messenger RNA; Methylation; Methyltransferase; Microscopy; Modeling; Molecular; Mutation; Nutrient availability; Oocytes; Oogenesis; Organism; Ovary; Pathway interactions; Phenotype; Polycystic Ovary Syndrome; Premature Ovarian Failure; Proteins; Puberty; RNA; RNA Binding; RNA Splicing; RNA-Binding Proteins; Regulation; Reiterated Genes; Reporter; Repression; Reproductive Biology; Reproductive Health; Research Personnel; Ribosomal DNA; Ribosomes; Role; Sex Chromosomes; Sex Differentiation; Sexual Development; Signal Transduction; Spermatogenesis; System; Testing; Testis; Training; Transcript; Transgenic Organisms; Translations; Validation; Vertebrates; Virilism; Y Chromosome; Zebrafish; autosome; detection of nutrient; gender dysphoria; gene conservation; gene product; genetic approach; gonad development; hormonal signals; insight; male; methylation pattern; mutant; nutrition; ovarian failure; posttranscriptional; preservation; programs; reproductive development; reproductive fitness; sex; sex determination; sex development disorder; translation factor

Project Summary Disorders of sexual development (DSDs) encompass a variety of congenital conditions that present with diverse phenotypes, such as virilization, gonadal dysgenesis, and delayed or absent puberty. In addition, affected individuals often suffer from secondary effects, including gender dysphoria and physical issues such as germ cell tumors and fertility disorders like polycystic ovarian syndrome or azoospermia. DSDs are the result of genetic, developmental, or hormonal anomalies that arise during embryogenesis and persist throughout sexual development and into adulthood. To better understand the etiology of DSDs, the role of RNA binding proteins in sex determination has been investigated due to their functions in controlling gene expression via post- transcriptional splicing, translational control, and mRNA localization. Identifying RNA binding protein RNA targets and characterizing these regulatory relationships is essential to further our understanding of mechanisms regulating sex determination. To study the events of sex determination and differentiation, our laboratory uses zebrafish, a genetically tractable model with high fecundity and rapid external development. Therefore, this powerful vertebrate system allows characterization of factors and pathways that are essential to reproductive development, successful fertility, and establishment and maintenance of the female gonad. The aims herein will identify conserved genes and mechanisms, that when disrupted, contribute to DSDs, fertility disorders, and cancers in humans. Specifically, the aims of this proposal will investigate the factors and mechanisms regulating sex-specific determination and differentiation in the context of a conserved vertebrate specific RNA binding protein and its targets. Further, completion of these aims will provide rigorous training in all aspects of genetic and molecular-based analyses, including generation, characterization, and validation of mutant and transgenic zebrafish lines, genomic cloning, and microscopy, which will foster my development as a successful independent investigator in the fields of developmental and reproductive biology.

项目总结