The crossing defects of integrin and Sin1/fry/trc mutant neurons illustrate the importance

of spatial restriction for a tiling system based on homotypic repulsion. For neurons normally tiling a 2D territory, without spatial restraints, INK 128 order repulsion would drive homologous dendrites to disperse into a 3D space with potentially considerable overlap of dendritic coverage in a given receptive field. In the case of Drosophila class IV da neurons, the restricted space is a 2D sheet between the basal surface of epidermal cells and the ECM. As highlighted by our study, tiling requires high precision in this spatial restriction: a slight deviation of dendrites from this 2D space is sufficient to circumvent homotypic repulsion and cause overlap of dendritic fields. What about other tiling systems? One vertebrate tiling system that has some similarity with the Drosophila class IV da neurons is the fish somatosensory neurons, which innervate the skin with axon arbors selleck compound ( Sagasti et al., 2005). Like the dendrites of class IV da neurons, these peripheral axons exhibit contact-dependent repulsion and expansion after ablation of adjacent neurons. It will be interesting to determine whether the processes of these sensory neurons are restricted to a 2D layer within the skin and whether the interaction of those neurites with ECM or skin cells are important for their

tiling. The vertebrate retina is a classical system for studying neuronal tiling. Certain types of retinal ganglion cells (RGCs) and amacrine cells perfectly tile the retina in the x-y plane. Ablation studies suggest that dendro-dendritic repulsion exists between dendrites of neighboring RGCs (Perry and Linden, 1982). The dendrites of RGCs and amacrine cells innervate various layers of retinal inner plexiform in a neuronal type-specific manner (Dacey et al., 2003, Kolb Ketanserin et al., 1992 and Mariani, 1990). It will be intriguing to find out whether the dendrites of a given type of ganglion cells or amacrine cells that tile are indeed restricted to a molecularly defined 2D layer(s) in the inner plexiform, and, if so, whether interactions

between cell adhesion molecules and the ECM contribute to the restricted dendritic distribution and tiling. Theoretically, spatial restraints should be a general prerequisite for homotypic repulsion, which may or may not be limited to 2D. Tiling of neuritic fields could conceivably be established by homotypic repulsion in restricted 3D spaces, such as columnar tiling of the transient neurites of murine retinal horizontal cells during postnatal development (Huckfeldt et al., 2009). However, besides spatial restraints, there could be additional mechanisms to enhance the effectiveness of homotypic repulsion in partitioning 3D neuritic fields. One potential mechanism is to have more homologous neurites within a given space, which would increase the possibility of neurite encounter and repulsion.