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Abstract

The acquisition of bilateral symmetry was a key evolutionary step, allowing the development of a centralized nervous system (CNS). However, the developmental signals that position bilateral symmetric structures in relation to the mid- line are still poorly understood. Planarian plasticity demands continuous positional information to maintain body pro- portions and axial information during regeneration and homeostasis. This ability offers us an ideal context to study the signals required to position the CNS in relation to the midline. Here we demonstrate that Wnt5 and Slit are axon repulsive cues in planarians which exert their function from opposite domains of the CNS. We found that the recep- tors ROR2 and ROBO-c, respectively, mediate their effect on axonal growth. Interestingly, ROR2 and ROBO-c are expressed in neurons but also in muscular cells that express slit and wnt5, respectively. Since muscular cells exert the positional control in planarians, we hypothesized that WNT5-ROR and SLIT-ROBO-c signals could conform a self-re- gulated system to define their expression boundaries in addition to guide the axonal path, allowing the self-mainte- nance of the medio-lateral positional information. We are currently modelling the biological data to deepen into the proposed model.