Establishment and Remodeling of Sexually Dimorphic Tissues: Immune Cell Contributions

[eng] Sex-specific differences established in the brain during early critical periods are thought to affect function and behavior later in life (Huang et al., 2024; Sofer et al., 2024; Waters & Simerly, 2009), but the mechanisms and cell types involved in the organization of the brain during development or in states of disease are not fully understood. It is also not known how interactions between the immune, endocrine, and nervous systems influence development, brain function, and behavior, or whether sexual dimorphism in microglia colonization and morphology like that observed in mammals also exists within brain regions of the adult zebrafish nervous system. Both reproductive and neurological disorders can arise from disruption of sexually dimorphic Tissues (reviewed in (TIoel et al., 2016; López-Otieda & Hurley, 2021; McCarthy, 2016)). It is then important to understand how gonad differentiation occurs, and to what extent it affects establishment of sex-specific brain organization during development, and maintenance in adulthood. Better describing how distinct cell types and their interactions influence a tissue and its function, and how they are altered in reproductive and sex-biased neurological disorders is key to understanding tIssue function in health and disease. AIMS AND HYPOTHESES: A. Investigate if cell death pathways promote ovarian failure and remodeling of the gonad. Hypothesis: Tumor suppressor factors contribute to sex-reversal by activating cell death pathways in the oocyte during ovarian failure. B. Examine if sex-reversal and acquisition of male specific traits require activation of macrophages. Hypothesi: AcJvaJon of macrophages by the germline and/or somatic gonadal cells drives remodeling of the ovary. C. Describe if microglia is necessary for establishment of brain sexual dimorphism during early development. Hypothesis: Microglia are required for the development of sex-specific differences between the female and male adult brains.