SUMMARYSubdivision of proliferating tissues into adjacent compartments that do not mix plays a key role in animal development. The Actin cytoskeleton has recently been shown to mediate cell sorting at compartment boundaries, and reduced cell proliferation in boundary cells has been proposed as a way of stabilizing compartment boundaries. Cell interactions mediated by the receptor Notch have been implicated in the specification of compartment boundaries in vertebrates and in Drosophila, but the molecular effectors remain largely unidentified. Here, we present evidence that Notch mediates boundary formation in the Drosophila wing in part through repression of bantam miRNA. bantam induces cell proliferation and we have identified the Actin regulator Enabled as a new target of bantam. Increased levels of Enabled and reduced proliferation rates contribute to the maintenance of the dorsal-ventral affinity boundary. The activity of Notch also defines, through the homeobox-containing gene cut, a distinct population of boundary cells at the dorsal-ventral (DV) interface that helps to segregate boundary from non-boundary cells and contributes to the maintenance of the DV affinity boundary.

Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues.

The Drosophila wing primordium is subdivided into a dorsal (D) and a ventral (V) compartment by the activity of the LIM-homeodomain protein Apterous in D cells. Cell interactions between D and V cells induce the activation of Notch at the DV boundary. Notch is required for the maintenance of the compartment boundary and the growth of the wing primordium. Beadex, a gain-of-function allele of dLMO, results in increased levels of dLMO protein, which interferes with the activity of Apterous and results in defects in DV axis formation. We performed a gain-of-function enhancer-promoter (EP) screen to search for suppressors of Beadex when overexpressed in D cells. We identified 53 lines corresponding to 35 genes. Loci encoding for micro-RNAs and proteins involved in chromatin organization, transcriptional control, and vesicle trafficking were characterized in the context of dLMO activity and DV boundary formation. Our results indicate that a gain-of-function genetic screen in a sensitized background, as opposed to classical loss-of-function-based screenings, is a very efficient way to identify redundant genes involved in a developmental process. I N multicellular organisms, initially homogenous sheets of cells are often subdivided into adjacent cell populations by the activity of certain transcription factors (reviewed in Irvine and Rauskolb 2001). In many cases, cell interactions between these populations lead to the restricted expression of signaling molecules at their boundaries, which organize growth and/or the pattern of nearby cells. The stability of these boundaries frequently relies on the acquisition of differential cell affinities between adjacent populations. When these boundaries behave as lineage restriction boundaries, these populations are called compartments (García-Bellido et al. 1973). The Drosophila wing primordium, a monolayered epithelium that gives rise to the adult wing and part of the thorax, is subdivided into an anterior and a posterior compartment by the activity of the homeodomain transcription factors Engrailed and Invected in posterior cells (García-Bellido and Santamaria 1972;Lawrence and Morata 1976;Tabata et al. 1995;Zecca et al. 1995). During larval development, the wing primordium suffers a secondary compartment subdivision. The activity of the LIMhomeodomain transcription factor Apterous (Ap) is responsible for this later subdivision into a dorsal (D) and a ventral (V) compartment (Diaz-Benjumea and Cohen 1993).Ap has three functions in wing development. It is responsible for the establishment of the Notch-dependent signaling center, the generation of a lineage restriction at the DV boundary, and the acquisition of a dorsal identity during cell differentiation. Ap exerts these functions through three classes of target genes. The complementary expression of Serrate and Delta, two ligands of the receptor Notch, to D and V cells, respectively, initiates a cascade of short-range cell interactions that lead to the activation of Notch at the DV boundary ( Figure 1B The activity of ...

During the development of a given organ, tissue growth and fate specification are simultaneously controlled by the activity of a discrete number of signalling molecules. Here, we report that these two processes are extraordinarily coordinated in the Drosophila wing primordium, which extensively proliferates during larval development to give rise to the dorsal thoracic body wall and the adult wing. The developmental decision between wing and body wall is defined by the opposing activities of two secreted signalling molecules, Wingless and the EGF receptor ligand Vein. Notch signalling is involved in the determination of a variety of cell fates, including growth and cell survival. We present evidence that growth of the wing primordium mediated by the activity of Notch is required for wing fate specification. Our data indicate that tissue size modulates the activity range of the signalling molecules Wingless and Vein. These results highlight a crucial role of Notch in linking proliferation and fate specification in the developing wing primordium.