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.
Highlights
Adult stem cells have the capacity to self-renew indefinitely and to generate differentiated cells to maintain and repair the tissue in which they are located
Sara endosomes are dispatched asymmetrically during ISC mitosis In order to study the division of intestinal stem cells, we developed primary culture conditions to perform live imaging of the adult Drosophila midgut
During physiology of adult Drosophila midgut, stem cell selfrenewal is essential to maintain a pool of dividing cells, which compensates the death of differentiated cells
Summary
Adult stem cells have the capacity to self-renew indefinitely and to generate differentiated cells to maintain and repair the tissue in which they are located. The formation of daughter cells with distinct developmental potentials depends on two major mechanisms: the regulation by a stem cell niche and/or the asymmetric distribution of cell fate determinants (Morrison and Spradling, 2008; Hsu and Fuchs, 2012). The directional targeting of signalling molecules to one of the two daughter cells leads to the adoption of a specialized cell fate. Intestinal stem cells were discovered in the adult Drosophila midgut (Micchelli and Perrimon, 2006; Ohlstein and Spradling, 2006).
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