Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances

Pietak, Alexis; Levin, Michael

doi:10.1016/j.pbiomolbio.2018.03.008

Cited by 36 publications

(38 citation statements)

References 168 publications

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“…Thus, physiological connectivity is the binding mechanism responsible for the appearance of larger unified Selves. The coordination of cells toward a single goal (body patterning) is now known to be in part controlled by the activity of bioelectric networks mediated by gap junctions Mathews and Levin, 2018;Mclaughlin and Levin, 2018;Pietak and Levin, 2018). Consistent with the isomorphism between patterning control and behavioral control, the same scale-up occurs in morphogenesis: subcellular chirality that determines morphology of single-cell A B…”

Section: A B Cmentioning

confidence: 93%

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

2019

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All epistemic agents physically consist of parts that must somehow comprise an integrated cognitive self. Biological individuals consist of subunits (organs, cells, and molecular networks) that are themselves complex and competent in their own native contexts. How do coherent biological Individuals result from the activity of smaller sub-agents? To understand the evolution and function of metazoan creatures' bodies and minds, it is essential to conceptually explore the origin of multicellularity and the scaling of the basal cognition of individual cells into a coherent larger organism. In this article, I synthesize ideas in cognitive science, evolutionary biology, and developmental physiology toward a hypothesis about the origin of Individuality: "Scale-Free Cognition." I propose a fundamental definition of an Individual based on the ability to pursue goals at an appropriate level of scale and organization and suggest a formalism for defining and comparing the cognitive capacities of highly diverse types of agents. Any Self is demarcated by a computational surface -the spatio-temporal boundary of events that it can measure, model, and try to affect. This surface sets a functional boundarya cognitive "light cone" which defines the scale and limits of its cognition. I hypothesize that higher level goal-directed activity and agency, resulting in larger cognitive boundaries, evolve from the primal homeostatic drive of living things to reduce stress -the difference between current conditions and life-optimal conditions. The mechanisms of developmental bioelectricity -the ability of all cells to form electrical networks that process informationsuggest a plausible set of gradual evolutionary steps that naturally lead from physiological homeostasis in single cells to memory, prediction, and ultimately complex cognitive agents, via scale-up of the basic drive of infotaxis. Recent data on the molecular mechanisms of pre-neural bioelectricity suggest a model of how increasingly sophisticated cognitive functions emerge smoothly from cell-cell communication used to guide embryogenesis and regeneration. This set of hypotheses provides a novel perspective on numerous phenomena, such as cancer, and makes several unique, testable predictions for interdisciplinary research that have implications not only for evolutionary developmental biology but also for biomedicine and perhaps artificial intelligence and exobiology.

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Section: A B Cmentioning

confidence: 93%

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

2019

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“…Spatiotemporal electrochemical patterns affect cytoskeletal dynamics and play a role in defining spatial coordinates of tissues and organs in several species [1][2][3][4][5][6][7][8]. Therefore, it is tempting to investigate V mem -and pH igradients in relation to cytoskeletal patterns in a Drosophila mutant with disturbed axial polarity.…”

Section: Introductionmentioning

confidence: 99%

Bioelectrical and cytoskeletal patterns correlate with altered axial polarity in the follicular epithelium of the Drosophila mutant gurken

Schotthöfer

Bohrmann

2020

BMC Dev Biol

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Background: Bioelectrical signals are known to be involved in the generation of cell and tissue polarity as well as in cytoskeletal dynamics. The epithelium of Drosophila ovarian follicles is a suitable model system for studying connections between electrochemical gradients, patterns of cytoskeletal elements and axial polarity. By interactions between soma and germline cells, the transforming growth factor-α homolog Gurken (Grk) establishes both the anteroposterior and the dorsoventral axis during oogenesis. Results: In the follicular epithelium of the wild-type (wt) and the polarity mutant grk, we analysed stage-specific gradients of membrane potentials (V mem) and intracellular pH (pH i) using the potentiometric dye DiBAC 4 (3) and the fluorescent pH-indicator 5-CFDA,AM, respectively. In addition, we compared the cytoskeletal organisation in the follicular epithelium of wt and grk using fluorescent phalloidin and an antibody against acetylated α-tubulin. Corresponding to impaired polarity in grk, the slope of the anteroposterior V mem-gradient in stage S9 is significantly reduced compared to wt. Even more striking differences in V mem-and pH i-patterns become obvious during stage S10B, when the respective dorsoventral gradients are established in wt but not in grk. Concurrent with bioelectrical differences, wt and grk exhibit differences concerning cytoskeletal patterns in the follicular epithelium. During all vitellogenic stages, basal microfilaments in grk are characterised by transversal alignment, while wt-typical condensations in centripetal follicle cells (S9) and in dorsal centripetal follicle cells (S10B) are absent. Moreover, in grk, longitudinal alignment of microtubules occurs throughout vitellogenesis in all follicle cells, whereas in wt, microtubules in mainbody and posterior follicle cells exhibit a more cell-autonomous organisation. Therefore, in contrast to wt, the follicular epithelium in grk is characterised by missing or shallower electrochemical gradients and by more coordinated transcellular cytoskeletal patterns. Conclusions: Our results show that bioelectrical polarity and cytoskeletal polarity are closely linked to axial polarity in both wt and grk. When primary polarity signals are altered, both bioelectrical and cytoskeletal patterns in the follicular epithelium change. We propose that not only cell-specific levels of V mem and pH i , or the polarities of transcellular electrochemical gradients, but also the slopes of these gradients are crucial for cytoskeletal modifications and, thus, for proper development of epithelial polarity.

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“…Anatomical polarity can be altered by bioelectric gradient dynamics . This is due to the spatial patterns of membrane polarization in planaria being important for regeneration, including in scaling and axial polarity; significant alteration of the bioelectric/biochemical circuits which normally guides cell behavior and distribution of regeneration‐guiding morphogens can be expected to alter the patterning outcome . In order to understand the establishment of anterior–posterior anatomical polarity and the role of ionic gradients therein, detailed measurements of electrical properties across this species of planaria will be needed, to compare and contrast against available data in the other model species.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ivermectin Exposure on Regeneration ofD. dorotocephalaPlanaria: Exploiting Human‐Approved Ion Channel Drugs as Morphoceuticals

Ferenc

Levin

2018

Macromolecular Bioscience

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Transformative applications in regenerative medicine await increased control of processes implementing repair and remodeling of complex living structures. Recent work reveals ion channel drugs as a powerful toolkit for modulating endogenous bioelectric circuits that control growth and form in vivo and in vitro. It is therefore especially important to develop assays in model systems that will enable the testing of these “morphoceuticals”—compounds with predictable effects on anatomical structure. The regenerative planaria are an ideal model system for this purpose. Several studies have shown a role for bioelectric signaling in planarian regeneration, but these have focused on Dugesia japonica and Schmidtea mediterranea. It is not known how the alterations of ion channel activity would affect regeneration in other species of planaria—an important aspect of building robust computational models of bioelectric circuits. Here, the effect of ivermectin (IVM), a chloride channel opener drug commonly used to combat heartworm is tested, on regeneration in a new species of planaria: Dugesia dorotocephala. Exposure to IVM during regeneration results in patterning abnormalities, such as bifurcated tails with partial heads, as well as delayed regeneration. These data extend our understanding of the effects of human‐approved ion channel drugs on regenerative processes.

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Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances

Cited by 36 publications

References 168 publications

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

The Computational Boundary of a “Self”: Developmental Bioelectricity Drives Multicellularity and Scale-Free Cognition

Bioelectrical and cytoskeletal patterns correlate with altered axial polarity in the follicular epithelium of the Drosophila mutant gurken

Effects of Ivermectin Exposure on Regeneration ofD. dorotocephalaPlanaria: Exploiting Human‐Approved Ion Channel Drugs as Morphoceuticals

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