Autocrine and paracrine Wingless signalling in the Drosophila midgut by both continuous gradient and asynchronous bursts of wingless expression

Wingless (Wg)/ Wnt signalling is a major regulator of homeostasis in both the mammalian andDrosophilaintestine. InDrosophilathe organisation and function of Wingless signalling in the adult intestine remain poorly understood. Here we characterise the pattern of expression ofwg, the stabilisation of its effector Armadillo in the adultDrosophilamidgut, and correlate them with the response of the cells to Wg signalling activation. We show that in normal homeostasis there is a gradient of Wingless signalling in the intestinal stem cell (ISC) and the undifferentiated progenitor cell (enteroblast, EB) populations along the posterior midgut, with a high point at the midgut-hindgut boundary (pylorus). This gradient results from a combination of two sources of Wingless: a distant source outside the epithelium (the pylorus) and a local one from the ISCs and EBs themselves. Altogether, our studies show that Wingless expression and signalling in the epithelium is not continuous, but operates through bursts that occur randomly in space and time.</ns4:p

The pronotum LIM-HD gene tailup is both a positive and a negative regulator of the proneural genes achaete and scute of Drosophila

Early in the development of the imaginal wing disc of Drosophila, the LIM-HD gene tailup (islet), together with the HD genes of the iroquois complex, specify the notum territory of the disc. Later, tailup has been shown to act as a prepattern gene that antagonizes formation of sensory bristles on the notum of this fly. It has been proposed that Tailup downregulates the expression of the proneural genes achaete and scute by interfering with factors needed to activate these genes in the dorsocentral and scutellar regions of the disc. By means of a clonal analysis performed with tailup null alleles, here we show that, on the one hand, tailup is necessary to prevent formation of extra macrochaetae on most of the 11 sites where these landmark bristles arise on the fly notum. On the other hand, tailup is required to activate achaete and scute at the dorsocentral region, probably by acting as an hexameric complex with the cofactor Chip and the transcriptional activator Sspd on the dorsocentral enhancer of the achaete–scute complex. In contrast, in the scutellar region Tailup acts downstream of achaete–scute, antagonizing the proneural function of these genes probably in cooperation with Chip. We conclude that tailup acts on bristle development by several, even antagonistic, mechanisms

tailup, a LIM-HD gene, and Iro-C cooperate in Drosophila dorsal mesothorax specification

The LIM-HD gene tailup (tup; also known as islet) has been categorised as a prepattern gene that antagonises the formation of sensory bristles on the notum of Drosophila by downregulating the expression of the proneural achaete-scute genes. Here we show that tup has an earlier function in the development of the imaginal wing disc; namely, the specification of the notum territory. Absence of tup function causes cells of this anlage to upregulate different wing-hinge genes and to lose expression of some notum genes. Consistently, these cells differentiate hinge structures or modified notum cuticle. The LIM-HD co-factors Chip and Ssdp are also necessary for notum specification. This suggests that Tup acts in this process in a complex with Chip and Ssdp. Overexpression of tup, together with araucan, a `pronotum' gene of the iroquois complex (Iro-C), synergistically reinforces the weak capacity of either gene, when overexpressed singly, to induce ectopic notum-like development. Whereas the Iro-C genes are activated in the notum anlage by EGFR signalling, tup is positively regulated by Dpp signalling. Our data support a model in which the EGFR and Dpp signalling pathways, with their respective downstream Iro-C and tup genes, converge and cooperate to commit cells to the notum developmental fate

Wnt-Notch signalling: An integrated mechanism regulating transitions between cell states

The activity of Wnt and Notch signalling is central to many cell fate decisions during development and to the maintenance and differentiation of stem cell populations in homeostasis. While classical views refer to these pathways as independent signal transduction devices that co-operate in different systems, recent work has revealed intricate connections between their components. These observations suggest that rather than operating as two separate pathways, elements of Wnt and Notch signalling configure an integrated molecular device whose main function is to regulate transitions between cell states in development and homeostasis. Here, we propose a general framework for the structure and function of the interactions between these signalling systems that is focused on the notion of ‘transition states’, i.e. intermediates that arise during cell fate decision processes. These intermediates act as checkpoints in cell fate decision processes and are characterised by the mixed molecular identities of the states involved in these processes

Tufted is a gain-of-function allele that promotes ectopic expression of the proneural gene amos in Drosophila

The Tufted1 (Tft 1) dominant mutation promotes the generation of ectopic bristles (macrochaetae) in the dorsal mesothorax of Drosophila. Here we show that Tft 1 corresponds to a gain-of-function allele of the proneural gene amos that is associated with a chromosomal aberration at 36F–37A. This causes ectopic expression of amos in large domains of the lateral-dorsal embryonic ectoderm, which results in supernumerary neurons of the PNS, and in the notum region of the third instar imaginal wing, which gives rise to the mesothoracic extra bristles. Revertants of Tft 1, which lack ectopic neurons and bristles, do not show ectopic expression of amos. One revertant is a loss-of-function allele of amos and has a recessive phenotype in the embryonic PNS. Our results suggest that both normal and ectopic Tft 1 bristles are generated following similar rules, and both are subjected to Notch-mediated lateral inhibition. The ability of Tft 1 bristles to appear close together may be due to amos having a stronger proneural capacity than that of other proneural genes like asense and scute. This ability might be related to the wild-type function of amos in promoting development of large clusters of closely spaced olfactory sensilla

Drosophila midgut homeostasis involves neutral competition between symmetrically dividing intestinal stem cells

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 self-renewal, these findings establish intriguing parallels with the mammalian system, and confirm Drosophila as a useful model for studying adult intestinal maintenance