Drosophilamidgut homeostasis involves neutral competition between symmetrically dividing intestinal stem cells

Abstract

The Drosophila adult posterior midgut has been identified as a powerful system in which to study mechanisms that control intestinal maintenance, in normal conditions as well as during injury or infection. Early work on this system has established a model of tissue turnover based on the asymmetric division of intestinal stem cells. From the quantitative analysis of clonal fate data, we show that tissue turnover involves the neutral competition of symmetrically dividing stem cells. This competition leads to stem-cell loss and replacement, resulting in neutral drift dynamics of the clonal population. As well as providing new insight into the mechanisms regulating tissue selfrenewal, these findings establish intriguing parallels with the mammalian system, and confirm Drosophila as a useful model for studying adult intestinal maintenance.

Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine

“…Like any stem cell population in a cycling tissue, the size of the ISC population can vary as a result of changes in the balance between symmetric renewal, asymmetric renewal and lineage-ending symmetric differentiation (de Navascues et al, 2012;O'Brien et al, 2011) (Fig. 4A).…”

“…ISCs can divide asymmetrically to produce one ISC and one transient progenitor cell, the enteroblast (EB), which directly differentiates into either an absorptive enterocyte (EC) or a hormone-producing enteroendocrine cell (EE) (Micchelli and Perrimon, 2006;Ohlstein and Spradling, 2006). Alternatively, ISCs can undergo a symmetric differentiation division to produce two enteroblasts or a symmetric renewal division to produce two ISCs (de Navascues et al, 2012;O'Brien et al, 2011). A relative increase in symmetric renewals drives the adaptive growth of the intestine in response to nutrition, and is associated with elevated insulin signaling (O'Brien et al, 2011).…”

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

“…ISCs can divide both symmetrically and asymmetrically. A combined approach of mathematical modeing and genetic experiments suggest that, as in the mouse intestinal epithelium (Snippert et al, 2010), ISCs in the adult Drosophila midgut can devide symetrically and stochastically give rise to either two stem cells or two differentiated daughter cells (de Navascues et al, 2012). On the other hand, integrin-dependent adhesion to the basal membrane-leading to apical localization of the Par complex-and assymetric localisation of Sara endosomes contribute to Notch signalling bias and assymetric division of ICSs to produce EBs (Goulas et al, 2012) (Montagne and Gonzalez-Gaitan, 2014).…”

L’intestin moyen de drosophile

“…Tout d'abord, les mécanismes à l'origine de l'activation asymétrique de la voie Notch dans une seule des deux cellules filles sont mal compris. Il a également été proposé que les CSI se divisent de manière symétrique [28][29][30]. Les deux nouvelles cellules souches produites n'activeraient pas la voie Notch.…”