PgmNr D150: The sexual identity of adult intestinal stem cells controls organ size and plasticity.

Authors:
B. Hudry; S. Khadayate; I. Miguel-Aliaga


Institutes
Imperial College London, London, GB.


Keyword: physiology of adult organs

Abstract:

Male and female animals often differ in their metabolism and physiology. Genetic sex determination factors are known to play a key role during development in the formation of reproductive organs and secondary sexual characteristics, which could indirectly lead to physiological differences between the sexes. However, less is known about the maintenance and possible roles of sex determination mechanisms in fully developed organs. We have used the Drosophila melanogaster intestine to investigate the nature and significance of intrinsic sex determination pathways in an adult somatic organ in vivo. We find that the adult intestinal epithelium displays extensive sex differences in expression of genes with roles in growth and metabolism. We have focused first on one cell subpopulation, the intestinal stem cells (ISCs), to characterize the molecular mechanisms involved, and to establish their functional significance. Cell-specific reversals of the sexual identity of adult ISCs uncovers that this identity has a key role in controlling organ size, reproductive plasticity and 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 doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, these 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, we have extended our characterization of these sex differences to cell types other than somatic stem cells. We find that the sexual identity of different - but lineage-related - cell types in the adult fly is maintained through different mechanisms, and are currently exploring the possible metabolic significance of such mosaicism.



Flybase Genetic Index:
1. FlyBase gene symbol: tra; FBgn: FBgn0003741