Female sexual behavior is a complex process regulated by multiple brain circuits and influenced by sex steroid hormones acting in the brain. Several regions in the hypothalamus have been implicated in the regulation of female sexual behavior although a complete circuitry involved in female sexual behavior is not understood. Fez family zinc finger 1 (Fezf1) gene is a brain specific gene that has been mostly studied in the context of olfactory development, although in a recent study, FEZF1 has been identified as one of the genes responsible for the development of Kallman syndrome. In the present study, we utilized shRNA approach to downregulate Fezf1 in the ventromedial nucleus of the hypothalamus (VMN) with the aim to explore the role of this gene. Adult female mice were stereotaxically injected with lentiviral vectors encoding shRNA against Fezf1 gene. Mice injected with shRNA against Fezf1 had significantly reduced female sexual behavior, presumably due to the downregulation of estrogen receptor alpha (ER?), as the number of ER?-immunoreactive cells in the VMN of Fezf1 mice was significantly lower in comparison to controls. However, no effect on body weight or physical activity was observed in mice with downregulated Fezf1, suggesting that the role of Fezf1 in the VMN is limited to the regulation of sexual behavior.
COBISS.SI-ID: 4402298
In an invited review paper, the project PI described recent developments in the field of sex determination.
COBISS.SI-ID: 4402810
The brain is undoubtedly the most complicated organ and although considerable progress has been made in the understanding of brain function, many unanswered questions remain. Different approaches are used to study brain function with the ultimate aim of understanding how brain structure and function are connected with the behavioral outcomes of the individual. Pioneering studies on sex differences in the brain started in the 1960s when sex differences in brain morphology and some structural differences were observed in model animals. Later, such studies were also introduced the clinical medicine, and many studies in humans suggest that the functional organization of the brain is not entirely alike in men and women. In 2001, the Institute of Medicine at National academy of Sciences in the US issued a statement that sex has a significant importance for understanding health and disease, and for understanding human physiology generally. This was an important step forward in recognizing that males and females are biologically different not only with regards to gonads and secondary sexual characteristics but also in the structure and, more importantly, the function of many other organs including the brain. In addition to methodological difficulties in studying the human brain, significant individual variability in brain structures complicates studies of sex differences in the brain, as some differences might differ more between individuals than between sexes, as was recently demonstrated. Because of these large differences between individuals within one sex/gender, term sexual allomorphism is usually used instead of sexual dimorphism in regard to the brain, taking into account this vast individual variability in brain structure. In this article, we will review the current understanding of sex differences in the brain, mostly focusing on preclinical animal studies. Firstly, the conventional hypothesis of brain sexual differentiation will be described followed by newer contributions to this field, focusing mainly on hormone-independent sex differences in the brain. The article is focused mostly on the limbic system, although sex differences have been described in other parts of the brain including the cortex and cerebellum, but these are beyond the scope of this review.
COBISS.SI-ID: 4175226
PI was invited to contribute a chapter about SF-1 gene for the book Encylopedia of signalling molecules, published by prestigious publisher Springer. This book is a comprehensive review of different signalling molecules regulating different aspects of cells and tissues. Gregor Majdic was invited to contribute as one of the world leading experts on SF-1 gene.
COBISS.SI-ID: 4436858
Network science is today established as a backbone for description of structure and function of various physical, chemical, biological, technological, and social systems. Here we review recent advances in the study of complex biological systems that were inspired and enabled by methods of network science. First, we present research highlights ranging from determination of the molecular interaction network within a cell to studies of architectural and functional properties of brain networks and biological transportation networks. Second, we focus on synergies between network science and data analysis, which enable us to determine functional connectivity patterns in multicellular systems. Until now, this intermediate scale of biological organization received the least attention from the network perspective. As an example, we review the methodology for the extraction of functional beta cell networks in pancreatic islets of Langerhans by means of advanced imaging techniques. Third, we concentrate on the emerging field of multilayer networks and review the first endeavors and novel perspectives offered by this framework in exploring biological complexity. We conclude by outlining challenges and directions for future research that encompass utilization of the multilayer network formalism in exploring intercellular communication patterns in tissues, and we advocate for network science being one of the key pillars for assessing physiological function of complex biological systems...
COBISS.SI-ID: 512746040