Last, we tested if integrin overexpression can rescue the tiling defects in fry and Sin1 mutants by examining the interface between v′ada and vdaB neurons. fry1/fry6 larvae show extensive overlap of v′ada and vdaB dendritic fields ( Figure 8L), which is also caused by noncontacting dendritic crossings ( Figures 8P and Bortezomib price 8Q). Overexpression of Mys and Mew in class
IV da neurons completely rescued this phenotype ( Figures 8M and 8P). We did not observe a significant increase of heteroneuronal crossings in Sin1e03756 mutant larvae at the v′ada/vdaB interface ( Figures 8N and 8P), but found a reduction of such crossings by overexpression of Mys and Mew ( Figures 
and 8P). It is worth noting that although integrins rescued both isoneuronal and heteroneuronal dendritic
crossing in fry mutant animals, they did not appear to rescue the overbranching phenotype ( Figures 8F and 8M), a defect associated with fry and trc that was shown to be independent of the crossing phenotype ( Emoto et al., 2004). Taken together, our results Dolutegravir price indicate that tiling mutants of the TORC2/Trc pathway cause dendritic crossings that result in overlapping dendritic fields primarily by releasing dendrites from their confinement to the 2D space specified by the ECM. Self-avoidance and tiling are fundamental mechanisms governing the proper patterning of dendritic fields. Both mechanisms involve homotypic repulsion of dendrites to ensure nonredundant coverage of dendritic fields. In principle, such repulsion could arise from contact-dependent repulsion and/or short-range diffusible repulsive signals. For Drosophila class IV da neuron, there is substantial evidence for the involvement of contact-dependent dendritic repulsion ( Hughes et al., 2007, Matthews et al., 2007 and Soba et al., 2007, this study). over For the contact-dependent dendritic repulsion to work with high fidelity, it is essential that growing dendrites encounter each other reliably when they enter a shared territory, which is only possible if they grow on the same substrate in a restricted
space such as a 2D sheet. In this study we demonstrate the dendrites of class IV da neurons mostly grow between the basal surface of the epidermal cells and the ECM secreted by the epidermis, which effectively limits the dendrites to a 2D sheet. This restriction is imposed by the interaction between neuronal integrins and epidermal cell-derived laminins in the ECM. Loss of this interaction leads to dendrites’ detachment from the ECM and increased enclosure of dendrites by epidermal cells. As a result, the dendrites are no longer restricted in a 2D space and can cross other dendrites without direct dendro-dendritic contacts. Conversely, increasing the adhesive force between dendrites and the ECM by supplying more integrins to the dendrites eliminates enclosure of dendrites in the epidermis.