FIGURE 6. Schematic model of GJ-mediated and neural signals during regeneration.

(A) Post-pharyngeal amputation generates a regenerating worm with pre-existing head and a posterior wound. Our data suggest that long-range signals –informing about the presence of a head within the fragment-travel from anterior (brain in yellow) to the posterior wound (white arrowheads) through two pathways: ventral nerve (VNC, red line) and GJ-mediated signals associated with VNC (blue line) and parenchymatic cells (light blue background). In all, untreated animals or animals exposed to GJ blocker (octanol) and animals with VNC disruption regeneration of the missing posterior area is recreated without polarity problems. However, in animals where both octanol treatment and VNC disruption take place, signals coming from anterior areas are disrupted, leading to abnormalities in polarity (bipolar animals). (B) Blastema fate determination in regenerating post-pharyngeal fragments with anterior and posterior-facing wounds. Instructive signals from anterior wound travel to posterior wound through the same pathways as in “A” but in this case the information carried is to inform about the anterior blastema formation that instruct neoblasts to form a posterior blastema. In animals exposed to octanol this information is altered and animals regenerate bipolar heads. In the case of VNC disruption alone most animals regenerate without problems. If both VNC are disrupted and GJ are inhibited, animals regenerate four heads. Specific cuts for VNC disruption are represented for each case.