scabrous Modifies Epithelial Cell Adhesion and Extends the Range of Lateral Signalling during Development of the Spaced Bristle Pattern in Drosophila

Abstract

The role of scabrous (sca) in the evenly spaced bristle pattern of Drosophila is explored. Loss-of-function of sca results in development of an excess of bristles. Segregation of alternately spaced bristle precursors and epidermal cells from a group of equipotential cells relies on lateral inhibition mediated by Notch and Delta (Dl). In this process, presumptive bristle precursors inhibit the neural fate of neighbouring cells, causing them to adopt the epidermal fate. We show that Dl, a membrane-bound ligand for Notch, can inhibit adjacent cells, in direct contact with the precursor, in the absence of Sca. In contrast, inhibition of cells not adjacent to the precursor requires, in addition, Sca, a secreted molecule with a fibrinogen-related domain. Over-expression of Sca in a wild-type background, leads to increased spacing between bristles, suggesting that the range of signalling has been increased. scabrous acts nonautonomously, and we present evidence that, during bristle precursor segregation, Sca is required to maintain the normal adhesive properties of epithelial cells. The possible effects of such changes on the range of signalling are discussed. We also show that the sensory organ precursors extend numerous fine cytoplasmic extensions bearing Dl molecules, and speculate on a possible role for these structures during signalling.

Scabrous and Gp150 are endosomal proteins that regulate Notch activity

“…Endocytosis has been proposed both to downregulate N activity and to promote N activity by removing inactive and inhibitory forms of both N and its ligands from the cell surface (Berdnik et al, 2002;Seugnet et al, 1997). Although our data are probably consistent with previous models for Sca function in increasing the sensitivity or range of N signaling (Baker and Zitron, 1995;Renaud and Simpson, 2001), both the idea that sca and gp150 are most important in cells where N signaling would otherwise be downregulated, and the location of their products away from the cell surface supports the view that these proteins specifically affect a downregulatory mechanism, rather than acting directly on N activation. As the ectopic N activity in the spl mutant depends on Dl (Li et al, 2003), we infer that sca and gp150 promote ligand-dependent N activation.…”

“…This hypothesis proved difficult to confirm, however, as sca mutations affected only a subset of Notch functions, had weaker effects than N null mutations, and as no direct interaction between the Sca and N proteins was demonstrated (Baker and Zitron, 1995;. More recently, other ideas have been proposed: that Sca acts to scaffold N to the extracellular matrix to downregulate N activity (Powell et al, 2001), acts to preserve epithelial structure within proneural regions and so enhance function of other N ligands (Renaud and Simpson, 2001), or acts Notch and Delta are required for lateral inhibition during eye development. They prevent a tenfold excess in R8 photoreceptor cell specification.…”

A dynamical model of ommatidial crystal formation

“…For example, more cells might be in contact across the entire depth of the epithelium than can be represented in a planar model, whether through filipodia (25,27) or through other complex packing geometries. Indeed, genetic mosaic studies suggest that Dl's nonautonomy extends beyond obviously adjacent cells (19,45). Our model can approximate all of these possibilities through lattice diffusion and degradation.…”

Morphogen transport

“…One such mechanism is the use of filopodial structures to mediate morphogen transport. There is precedence that such cellular extensions serve to explore the environment, to detect distant signals or to present information to other cells (see Box 4) (Gustafson, 1964;Gustafson and Wolpert, 1967;Karp and Solursh, 1985;Bentley and ToroianRaymond, 1986;Locke, 1987;Miller et al, 1995;Jacinto et al, 2000;Vasioukhin et al, 2000;Milán et al, 2001;Renaud and Simpson, 2001;Sato and Kornberg, 2002;Wolf et al, 2002;De Joussineau et al, 2003;Rørth, 2003;Gallo and Letourneau, 2004;Yuste and Bonhoeffer, 2004;Lehmann et al, 2005;Demontis and Dahmann, 2007;Kress et al, 2007;Cohen et al, 2010;Swaney et al, 2010;Callejo et al, 2011;Cohen et al, 2011;Inaba et al, 2012;Peng et al, 2012;Rojas-Ríos et al, 2012;Vitriol and Zheng, 2012). The cytoneme model builds on these observations and postulates that long dynamic filopodia-like structures known as cytonemes project from target cells and contact morphogen-producing cells.…”