The sexual identity of adult intestinal stem cells controls organ size and plasticity
Genetic sex determination factors are known to play a key role in the development of reproductive organs. These sex differences, in turn, often lead to secondary sexual characteristics and physiological differences between the sexes. Less is known, however, about the maintenance and possible roles of genetic sex determination mechanisms in fully developed, non-gonadal organs.
I am using the Drosophila melanogaster intestine to investigate the nature and significance of intrinsic sex determination pathways in an adult somatic organ in vivo. I find that the adult intestinal epithelium displays extensive sex differences in expression of genes with roles in growth and metabolism. Focusing on the intestinal stem cells (ISCs), an epithelial cell subpopulation, I recently established that cell- and adult-stage specific reversals of their sexual identity affect organ size, its reproductive plasticity and its response to tumorigenic insults. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in ISC behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new branch of the sex differentiation pathway. Together, my findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism, which may be active in more tissues than previously recognized.
More recently, I have extended my characterization of these sex differences to intestinal cell types other than the somatic stem cells: enterocytes and entero-endocrine cells. I find that the sexual identity of these different - but lineage-related - cell types in the adult fly gut is maintained through different mechanisms, and am currently exploring the metabolic significance of such mosaicism.