Editors' ChoiceNeuroscience

Epidermal signals confine dendrites

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Science Signaling  23 Feb 2016:
Vol. 9, Issue 416, pp. ec38
DOI: 10.1126/scisignal.aaf5013

Guidance cues, such as semaphorins, help wire the nervous system during development. Dendrites, branchlike extensions of neuron cell bodies, mediate the location and strength of synaptic or sensory inputs, and defects in dendritic branch patterning are associated with various neurodevelopmental disorders. Contact-mediated repulsion (called “self-avoidance” and “tiling”) ensures dendritic branches from neighboring neurons do not overlap and redundantly cover the same synaptic space. Meltzer et al. found that signaling from epidermal-derived Sema-2b promotes self-avoidance by triggering integrin signaling in Drosophila sensory neurons. Dendrites of class IV dendritic arborization (da) sensory neurons are tightly confined between the basal surface of epidermal cells and the extracellular matrix (ECM). In vivo high-resolution confocal imaging revealed that dendrites of da sensory neurons in sema-2b (but not sema-2a) mutants exhibited extensive crossing and did not contact with ECM. Assessment of the developmental timing of these phenotypes suggested that Sema-2b promotes the maintenance of dendrite-ECM attachment in established neurons. Reporter analysis in flies indicated that sema-2b was expressed in epidermal cells, and restoring Sema-2b in the epidermis, but not in class IV da neurons, rescued the dendritic crossing defects observed in the sema-2b mutants. Knocking down PlexB, a receptor for Sema-2b, specifically in da neurons increased the number of dendritic crossings. In class IV da neurons, loss of the kinase Trc (Tricornered), which mediates integrin signaling, increases dendritic self-crossings and defects in dendrite-ECM adhesion. Trc activation (phosphorylation) in da neurons was reduced in sema-2b or plexB mutant flies, and overexpression of a constitutively active construct of Trc (but not wild-type or a nonphosphorylatable mutant) rescued the dendritic crossing defect in sema-2b mutants. Overexpressing integrin subunits, in particular a β subunit encoded by mys, greatly reduced the number of noncontacting dendritic crossings in sema-2b mutants. Furthermore, Mys colocalized with PlexB on the surface of Drosophila S2 cells in culture and da neurons in vivo. The findings indicate that Sema-2b/PlexB signaling promotes dendrite-ECM adhesion to promote contact-mediated self-avoidance during development.

S. Meltzer, S. Yadav, J. Lee, P. Soba, S. H. Younger, P. Jin, W. Zhang, J. Parrish, L. Y. Jan, Y.-N. Jan, Epidermis-derived semaphorin promotes dendrite self-avoidance by regulating dendrite-substrate adhesion in Drosophila sensory neurons. Neuron 89, 741–755 (2016). [PubMed]

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