We show that regenerating planarians' normal anterior-posterior pattern can be permanently rewritten by a brief perturbation of endogenous bioelectrical networks. Temporary modulation of regenerative bioelectric dynamics in amputated trunk fragments of planaria stochastically results in a constant ratio of regenerates with two heads to regenerates with normal morphology. Remarkably, this is shown to be due not to partial penetrance of treatment, but a profound yet hidden alteration to the animals' patterning circuitry. Subsequent amputations of the morphologically normal regenerates in water result in the same ratio of double-headed to normal morphology, revealing a cryptic phenotype that is not apparent unless the animals are cut. These animals do not differ from wild-type worms in histology, expression of key polarity genes, or neoblast distribution. Instead, the altered regenerative bodyplan is stored in seemingly normal planaria via global patterns of cellular resting potential. This gradient is functionally instructive, and represents a multistable, epigenetic anatomical switch: experimental reversals of bioelectric state reset subsequent regenerative morphology back to wild-type. Hence, bioelectric properties can stably override genome-default target morphology, and provide a tractable control point for investigating cryptic phenotypes and the stochasticity of large-scale epigenetic controls.
Regeneration is regulated not only by chemical signals but also by physical processes, such as bioelectric gradients. How these may change in the absence of the normal gravitational and geomagnetic fields is largely unknown. Planarian flatworms were moved to the International Space Station for 5 weeks, immediately after removing their heads and tails. A control group in spring water remained on Earth. No manipulation of the planaria occurred while they were in orbit, and space‐exposed worms were returned to our laboratory for analysis. One animal out of 15 regenerated into a double‐headed phenotype—normally an extremely rare event. Remarkably, amputating this double‐headed worm again, in plain water, resulted again in the double‐headed phenotype. Moreover, even when tested 20 months after return to Earth, the space‐exposed worms displayed significant quantitative differences in behavior and microbiome composition. These observations may have implications for human and animal space travelers, but could also elucidate how microgravity and hypomagnetic environments could be used to trigger desired morphological, neurological, physiological, and bacteriomic changes for various regenerative and bioengineering applications.
Early rapid strength production of the hip extensor muscles may be a sensitive and effective measure for discriminating between elderly females of different fall histories. These findings may provide important insight regarding implications for the assessment of fall risk and in the development of proper training programs aimed at minimizing the occurrence of falls and other balance-related injuries in the elderly.
SummaryPlanarian flatworms have been used for over a century as models for regeneration. Planarians live in aquatic environments with constant exposure to microbes, but the mechanisms by which bacteria may mediate planarian regeneration are largely unknown. We characterized the microbiome of laboratory populations of the planarian Dugesia japonica and determined how individual bacteria impact D. japonica regeneration. Eight to ten taxa in the phyla Bacteroidetes and Proteobacteria consistently occur across planarian colonies housed in different research laboratories. Individual members of the D. japonica microbiome can delay regeneration including the development of eye spots and blastema formation. The microbial metabolite indole is produced in significant quantities by two bacteria that are consistently found in the D. japonica microbiome and contributes to delays in regeneration. Collectively, these results provide a baseline understanding of the bacteria associated with the planarian D. japonica and demonstrate how metabolite production by host-associated microbes can affect regeneration.
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