Editors' ChoiceNeuroscience

Dscam Mediates Dendritic Self-Avoidance

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Science's STKE  08 May 2007:
Vol. 2007, Issue 385, pp. tw158
DOI: 10.1126/stke.3852007tw158

Three groups, Soba et al., Hughes et al., and Matthews et al., have implicated Dscam in dendritic self-avoidance of dendritic arborization (da) neurons in Drosophila larvae. Typically, different branches of the often-elaborate dendritic arborization of a particular neuron avoid contacting each other, a phenomenon called self-avoidance. Similarly, the dendrites of certain classes of neurons avoid those of neurons of the same type (tiling), although they may coexist with dendrites of neurons from different classes (see Kidd and Condron). In insects, the gene Dscam (Down’s syndrome cell adhesion molecule) can encode 38,016 distinct isoforms, which exhibit isoform-specific homophilic interactions; the particular isoform repertoire expressed in a given neuron is distinct from that of its neighbors (see Zinn). Dscam was expressed in all four classes of da neurons; elimination of its activity in individual neurons abrogated dendritic self-avoidance so that sister branches crossed each other and ran in bundles. Expression of single Dscam isoforms rescued self-avoidance, an effect that required the intracellular domain. However, Pak (p21-activated protein kinase), which mediates some downstream effects of Dscam, did not appear to be involved. Overexpression of the same Dscam isoform in neurons that would not otherwise avoid each other elicited avoidance of neighboring dendrites. Indeed, overexpression of a common Dscam isoform across classes or in all da neurons or expression of a single isoform in all da neurons of Dscam mutant larvae led to interclass dendritic avoidance. In contrast to its effects on self-avoidance, loss of Dscam function in these neurons failed to affect tiling in class III and IV da neurons. Moreover, mutation of components of a signaling pathway implicated in tiling failed to affect self-avoidance in class I, II, and III da neurons or dendritic bundling in class IV da neurons. All three groups concluded that the mechanisms involved in Drosophila dendritic self-avoidance are distinct from those that mediate tiling, with Dscam playing a critical role in self-avoidance. Diversity of Dscam isoforms may enable individual neurons to distinguish their own dendrites from those of their neighbors and respond appropriately.

M. E. Hughes, R. Bortnick, A. Tsubouchi, P. Bäumer, M. Kondo, T. Uemura, D. Schmucker, Homophilic Dscam interactions control complex dendrite morphogenesis. Neuron 54, 417-427 (2007). [Online Journal]

P. Soba, S. Zhu, K. Emoto, S. Younger, S.-J. Yang, H.-H. Yu, T. Lee, L. Y. Jan, Y.-N. Jan, Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization. Neuron 54, 403-416 (2007). [Online Journal]

B. J. Matthews, M. E. Kim, J. J. Flanagan, D. Hattori, J. C. Clemens, S. L. Zipursky, W. B. Grueber, Dendrite self-avoidance is controlled by Dscam. Cell 129, 593-604 (2007). [Online Journal]

T. Kidd, B. Condron, Avoiding the SCAMs. Neuron 54, 350-352 (2007). [Online Journal]

K. Zinn, Dscam and neuronal uniqueness. Cell 129, 455-456 (2007). [Online Journal]

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