One scenario that might explain these observations is that Dscam1 mutations lead to defects in contact-mediated repulsion in class IV neurons that are manifest primarily as bundles and clusters

buy INCB018424 of crossings. Noncontacting crossings might arise with certain probability elsewhere due to enclosure of class IV dendrites. Tight clustering of dendrites in Dscam clones could also conceivably have a secondary effect of enhancing apparent noncontacting crossings within crossing clusters if bundling precedes ingression. Together, these results suggest that integrins support self-avoidance by promoting the positioning of dendrites on the basal surface of the epidermis, where sister dendrites can reliably recognize and repel each other through the action of Dscam1. The molecular interplay

between growing dendrites, Antidiabetic Compound Library ECM, and surrounding cells is likely intricate and relevant for diverse morphological and functional properties of dendrites. We provide evidence that da sensory neurons in Drosophila develop a complex spatial relationship with the ECM and epidermis that is under the control of integrin receptors. Our results further suggest that the relationships that are established between dendrites and their substrate have important implications for dendritic morphology, self-avoidance, and maintenance. EM analysis indicated that larval da neuron dendrites can reside either on the basal surface of epidermal cells in contact with ECM or intermittently enclosed within epidermal invaginations. Enclosed dendrites appear separated from the extracellular space by sheets of closely apposed epidermal cell membrane that originate at the basal surface. Based on marker expression, these arbors can become enclosed along major proximal regions, and also intermittently along higher-order branches. By contrast, terminal endings may remain

on the basal surface of the epidermis. Within the enclosure, epidermal and dendritic membranes appeared to be closely juxtaposed. A prior TEM study in blowfly described ensheathment Cell press of dendrites by glia containing fluid-filled spaces, and termination of dendrites within epidermal invaginations (Osborne, 1964). These differences might point to additional diversity in dendrite-epidermal relationships, perhaps arising due to differences in the identities (or regions) of the sensory neurons examined, or perhaps species differences. An important goal will be to identify additional markers to extend this characterization, as well as examine other molecules at the dendrite-epidermal interface for possible roles in the establishment or maintenance of specific interactions. Our results provide molecular insight into how dendrites at the basal surface are segregated from enclosed dendrites. Loss of integrin function in neurons increases dendrite enclosure according to marker expression, whereas neuronal overexpression of integrins has the opposite effect, diminishing markers of enclosure along class IV dendrites.