Functional characterization of new sex pathways downstream of the female sex determinant TraF ; Caractérisation fonctionnelle de nouvelles voies de différenciation sexuelle en aval du déterminant sexuel femelle TraF

Sex differences are widespread in the animal kingdom. While males and females differ in their reproductive organs and primary sex characteristics, they also exhibit distinct morphological, physiological and behavioral traits. While the role of sex hormones in driving these somatic differences is well understood, the direct influence of sex chromosomes remains less clear. Although some studies suggest that the intrinsic presence of sex chromosomes, known as cellular sex, contributes to certain sex differences, where and how cellular sex affects somatic cells is still largely unknown.In Drosophila, cellular sex plays a crucial role in reproductive-related differences, such as the development of sex organs, pheromone secretion, and courtship behavior. These processes are mediated by a canonical sex differentiation pathway downstream of the female determinant TransformerF (TraF), whose effectors, Doublesex (Dsx) and Fruitless (Fru), are active only in sex organs and other reproductive tissues. However, recent findings have shown that cellular sex can influence the function of certain cells even if they do not express dsx and fru.Notably, my team demonstrated that the sexual identity of adult intestinal stem cells, determined by the presence or absence of TraF, regulates their proliferative capacity independently of Dsx and Fru. These results provide proof of principle for the existence of new sex differentiation pathways downstream of TraF. The goal of my thesis was to assess the global importance of these new pathways and to uncover the cellular and molecular mechanisms through which cellular sex exerts its influence.Using advanced genetic tools, I revealed that all somatic cells interpret the intrinsic presence of sex chromosomes by actively producing the female sex determinant TraF. This widespread occurrence of cellular sex is essential for sexual differentiation. Specifically, I showed that the new sex pathways downstream of TraF are both necessary and sufficient to control sex differences in organ size and ...