ABSTRACT
Tissue homeostasis is maintained by adult stem cells, which self-renew and give rise to differentiating cells. The generation of daughter cells with different fates is mediated by signalling molecules coming from an external niche or being asymmetrically dispatched between the two daughters upon stem cell mitosis. In the adult Drosophila midgut, the intestinal stem cell (ISC) divides to generate a new ISC and an enteroblast (EB) differentiating daughter. Notch signalling activity restricted to the EB regulates intestinal cell fate decision. Here, we show that ISCs divide asymmetrically, and Sara endosomes in ISCs are specifically dispatched to the presumptive EB. During ISC mitosis, Notch and Delta traffic through Sara endosomes, thereby contributing to Notch signalling bias, as revealed in Sara mutants: Sara itself contributes to the control of the ISC asymmetric division. Our data uncover an intrinsic endosomal mechanism during ISC mitosis, which participates in the maintenance of the adult intestinal lineage.
Subject(s)
Adult Stem Cells/cytology , Cell Division/physiology , Drosophila Proteins/metabolism , Drosophila melanogaster/cytology , Endosomes/metabolism , Intestines/cytology , Transforming Growth Factor beta/metabolism , Adult Stem Cells/physiology , Animals , Animals, Genetically Modified , Cell Lineage/genetics , Cell Polarity/physiology , Drosophila Proteins/genetics , Drosophila melanogaster/metabolism , Intestinal Mucosa/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Mitosis/physiology , Protein Transport/genetics , Receptors, Notch/metabolism , Transforming Growth Factor beta/geneticsABSTRACT
Here we investigate the structural and functional basis of the interactions between Notch and Wingless signalling in Drosophila. Using yeast-two-hybrid and pull-down assays we show that Notch can bind directly a form of Dishevelled that is stabilized upon Wingless signalling. Moreover, we show that the mechanism by which Wingless signalling is able to downregulate Notch is by promoting its ligand-independent traffic to a compartment where it is degraded and that this activity depends on Dishevelled.
