Dscam Proteins Direct Dendritic Targeting through Adhesion

• Published in: Neuron (Cambridge, Mass.) Vol. 89; no. 3; pp. 480 - 493
• Main Authors: Tadros, Wael, Xu, Shuwa, Akin, Orkun, Yi, Caroline H., Shin, Grace Ji-eun, Millard, S. Sean, Zipursky, S. Lawrence
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.02.2016; Elsevier Limited
• Subjects: Adhesion; Adhesives; Alleles; Animals; Cell Adhesion - genetics; Cell Adhesion - physiology; Cell growth; Cloning; Dendrites - physiology; Drosophila melanogaster; Drosophila Proteins - biosynthesis; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Gene Expression Regulation, Developmental - physiology; Mosaicism; Neural Cell Adhesion Molecules - biosynthesis; Neural Cell Adhesion Molecules - genetics; Neural Cell Adhesion Molecules - physiology; Neurons; Proteins
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.12.026

Cell recognition molecules are key regulators of neural circuit assembly. The Dscam family of recognition molecules in Drosophila has been shown to regulate interactions between neurons through homophilic repulsion. This is exemplified by Dscam1 and Dscam2, which together repel dendrites of lamina neurons, L1 and L2, in the visual system. By contrast, here we show that Dscam2 directs dendritic targeting of another lamina neuron, L4, through homophilic adhesion. Through live imaging and genetic mosaics to dissect interactions between specific cells, we show that Dscam2 is required in L4 and its target cells for correct dendritic targeting. In a genetic screen, we identified Dscam4 as another regulator of L4 targeting which acts with Dscam2 in the same pathway to regulate this process. This ensures tiling of the lamina neuropil through heterotypic interactions. Thus, different combinations of Dscam proteins act through distinct mechanisms in closely related neurons to pattern neural circuits. •Dscam2 patterns L4 dendrites by targeting them to a fascicle of other lamina neurons•This requires homophilic interactions between Dscam2 in L4 and the target fascicle•Single-cell genetic mosaics and live imaging suggest these interactions are adhesive•Dscam4 functions in the same pathway to direct dendritic targeting Drosophila Dscam receptors were known to regulate neural circuit assembly using homophilic repulsion. Tadros et al. show that the Dscams use homophilic adhesion to direct dendritic targeting, revealing this family can use different molecular mechanisms to pattern closely related neurons.