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Researchers Reveal Signaling Integration Underlying Asymmetrical Neurite Outgrowth
When axons navigate through a complex in vivo environment, at any given point they are probably confronted with several different guidance cues. Given the large number of different axon trajectories, it remains an enduring mystery how wiring specificity is achieved by a limited repertoire of secreted molecules.
The recent work by WANG Jiaming and DING Mei from the Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences, suggests combinatorial interactions that could help, in part, explain cell-specific response to guidance signals.
Both Slit-Robo and Wnt-Ror pathways are involved in proper neurite extension, but whether and how these two signaling pathways are interacted is largely unknown. WANG and DING found that instead of mediating Slit signaling, Robo could bind and respond to Wnt ligand. By forming a complex with the Ror receptor and Dsh effector, Robo receptor promotes signal transduction from Wnt to Dsh. Intriguingly, Dsh is asymmetrically distributed and the asymmetric distribution of Dsh is dependent on Robo, but not Ror receptor or Wnt ligand.
Ror receptor was recently identified as a core component in PCP (planar cell polarity) pathway. The PCP pathway is critical for the generation of both global and local directional information, which is the key to breaking symmetry and creating the complex organizational pattern of living organisms. The asymmetric subcellular localization of Dsh is tightly linked to the polarized action of a cell.
The fact that Robo but not Ror or Wnt is specifically participated in the establishment of a polarized signaling apparatus centered on Dsh suggests a unique role of Robo for converting the unevenly distributed Wnt signal to a polarized intracellular response in vivo.
Considering both Slit and Wnt signals are widely implicated in multiple cellular development processes and likely talk to each other at various places and times, this study will have profound influence on fundamental aspects of cellular and developmental biology in general.
This work entitled “Robo and Ror function in a common receptor complex to regulate Wnt-mediated neurite outgrowth in Caenorhabditis elegans” was online published in PNAS (
Figure. The Robo-Ror receptor complex functions in Wnt-mediated neurite outgrowth (Image by IGDB)