Figure 4. Permanent change to planarian target morphology: resetting bioelectrical pattern memories.

(A) Exposing planarian fragments to the gap junction blocker 1-octanol for three days results in a permanent re-setting of the target morphology [193]. Trunk fragments of such worms continue to regenerate as double-headed animals in perpetuity, in plain water. 1-octanol is washed out of the worm tissues within 2–3 days (as shown by mass spectrometry), this demonstrates transient physiological changes becoming consolidated as long-term pattern memory, without genomic editing. The animals’ target morphology can be re-set back to normal by altering the bioelectric circuit back to a wild-type distribution, using ion pump drugs such as SCH28080 (A′).

(B) Animals that did not become double-headed after an initial exposure to 1-octanol are not wild-type because when cut in plain water they give rise to the same percentage of double-headed worms in each generation. Here shown as a state transition diagram with double-headed worms always regenerating as double-headed (a terminal state) while cryptics continue to generate double-headed worms at the same ratio (each arrow is labeled with the reagent applied at regeneration and the percentage of outcomes).

(B′) Cryptic worms are identical to wild-type worms in their anatomy, expression of head and tail marker, and stem cell distribution [132]. However, a uniform depolarization of endogenous bioelectrical gradient reveals the difference between normal and cryptic animals. This altered bioelectric distribution is the key functional component of the re-writable pattern memory mediating the regenerative control.

(C) The same body can contain at least two diverse bioelectric patterns guiding future growth: wild-type (permanent single1-headed) or cryptic (destabilized, stochastic). One way to understand stable, discrete anatomical outcomes emerging from bioelectric circuit activity is as stable attractors in a morphospace defined by the voltage states of the two ends of the body.

Panel C made by Jeremy Guay of Peregrine Creative.