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Publication : Dendrite self-avoidance requires cell-autonomous slit/robo signaling in cerebellar purkinje cells.

First Author  Gibson DA Year  2014
Journal  Neuron Volume  81
Issue  5 Pages  1040-1056
PubMed ID  24607227 Mgi Jnum  J:221288
Mgi Id  MGI:5638834 Doi  10.1016/j.neuron.2014.01.009
Citation  Gibson DA, et al. (2014) Dendrite self-avoidance requires cell-autonomous slit/robo signaling in cerebellar purkinje cells. Neuron 81(5):1040-56
abstractText  Dendrites from the same neuron usually develop nonoverlapping patterns by self-avoidance, a process requiring contact-dependent recognition and repulsion. Recent studies have implicated homophilic interactions of cell surface molecules, including Dscams and Pcdhgs, in self-recognition, but repulsive molecular mechanisms remain obscure. Here, we report a role for the secreted molecule Slit2 and its receptor Robo2 in self-avoidance of cerebellar Purkinje cells (PCs). Both molecules are highly expressed by PCs, and their deletion leads to excessive dendrite self-crossing without affecting arbor size and shape. This cell-autonomous function is supported by the boundary-establishing activity of Slit in culture and the phenotype rescue by membrane-associated Slit2 activities. Furthermore, genetic studies show that they act independently from Pcdhg-mediated recognition. Finally, PC-specific deletion of Robo2 is associated with motor behavior alterations. Thus, our study uncovers a local repulsive mechanism required for self-avoidance and demonstrates the molecular complexity at the cell surface in dendritic patterning.
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