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Long-Term, Stochastic Editing of Regenerative Anatomy via Targeting Endogenous Bioelectric Gradients.
Fallon Durant1, Junji Morokuma1, Christopher Fields2
1Allen Discovery Center at Tufts University, and Department of Biology, Tufts University, Medford, Massachusetts.
Biophysical Journal
|May 25, 2017
Summary
Planarian regeneration can be permanently altered by briefly changing their bioelectrical networks, leading to a stable, hidden change in how they regrow. This epigenetic switch, controlled by cellular resting potential, affects future regeneration patterns.
Area of Science:
- Developmental Biology
- Regenerative Medicine
- Epigenetics
Background:
- Planarian regeneration relies on complex patterning mechanisms.
- The role of bioelectrical networks in stable pattern alteration is not well understood.
- Cryptic phenotypes can be revealed under specific conditions.
Purpose of the Study:
- To investigate if endogenous bioelectrical networks can permanently alter planarian regeneration.
- To understand the mechanisms behind stable epigenetic control of morphology.
- To explore the concept of cryptic phenotypes in regeneration.
Main Methods:
- Perturbation of endogenous bioelectrical networks in amputated planarian trunk fragments.
- Analysis of regenerative morphology ratios (two-headed vs. normal).
- Subsequent amputations to reveal cryptic phenotypes.
- Assessment of histology, gene expression, and neoblast distribution.
- Measurement of cellular resting potential patterns.
Main Results:
- Temporary bioelectrical network modulation induced a stable, stochastic ratio of two-headed to normal regenerates.
- This alteration was a profound, hidden change in patterning circuitry, not partial penetrance.
- Morphologically normal regenerates exhibited a cryptic phenotype, consistently producing the same ratio upon re-amputation.
- Altered regenerative body plan was stored via global cellular resting potential patterns, acting as an epigenetic switch.
- Experimental reversal of bioelectric state reset regeneration to wild-type.
Conclusions:
- Bioelectrical properties can stably override genome-default target morphology during regeneration.
- Cellular resting potential patterns represent a multistable epigenetic mechanism for anatomical control.
- This study provides a model for investigating cryptic phenotypes and stochastic epigenetic controls in large-scale patterning.
