Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions

Cervera, Javier; Meseguer, Salvador; Levin, Michael; Mafé, Salvador

doi:10.1016/j.bioelechem.2019.107410

Cited by 14 publications

(10 citation statements)

References 33 publications

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“…Similarly, individual cells homeostatically maintain V mem (cell membrane resting potential voltage) levels. However, cells can electrically couple via gap junctions to create bioelectric networks that work as a kind of virtual governor—coupled oscillators possess emergent dynamics that now maintain large, spatial patterns of V mem against perturbation with greater stability ( Pietak and Levin, 2017 , 2018 ; Cervera et al, 2018 , 2019a , b , 2020a , b ; Pai et al, 2018 ; Manicka and Levin, 2019a ). These spatial patterns serve as instructive pattern memories guiding the activity of a cell collective through anatomical morphospace toward the correct target morphology ( Sullivan et al, 2016 ; Levin, 2021a ; Pezzulo et al, 2021 ).…”

Section: Somatic Cognition: An Example Of Unconventional Agency In De...mentioning

confidence: 99%

Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds

Levin

2022

Front. Syst. Neurosci.

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135

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Synthetic biology and bioengineering provide the opportunity to create novel embodied cognitive systems (otherwise known as minds) in a very wide variety of chimeric architectures combining evolved and designed material and software. These advances are disrupting familiar concepts in the philosophy of mind, and require new ways of thinking about and comparing truly diverse intelligences, whose composition and origin are not like any of the available natural model species. In this Perspective, I introduce TAME—Technological Approach to Mind Everywhere—a framework for understanding and manipulating cognition in unconventional substrates. TAME formalizes a non-binary (continuous), empirically-based approach to strongly embodied agency. TAME provides a natural way to think about animal sentience as an instance of collective intelligence of cell groups, arising from dynamics that manifest in similar ways in numerous other substrates. When applied to regenerating/developmental systems, TAME suggests a perspective on morphogenesis as an example of basal cognition. The deep symmetry between problem-solving in anatomical, physiological, transcriptional, and 3D (traditional behavioral) spaces drives specific hypotheses by which cognitive capacities can increase during evolution. An important medium exploited by evolution for joining active subunits into greater agents is developmental bioelectricity, implemented by pre-neural use of ion channels and gap junctions to scale up cell-level feedback loops into anatomical homeostasis. This architecture of multi-scale competency of biological systems has important implications for plasticity of bodies and minds, greatly potentiating evolvability. Considering classical and recent data from the perspectives of computational science, evolutionary biology, and basal cognition, reveals a rich research program with many implications for cognitive science, evolutionary biology, regenerative medicine, and artificial intelligence.

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Section: Somatic Cognition: An Example Of Unconventional Agency In De...mentioning

confidence: 99%

Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds

Levin

2022

Front. Syst. Neurosci.

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135

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“…However, transcription of these genes does not necessarily entirely define the bioelectric state of blastema cells. Bioelectric state is controlled not only by the transcriptional or translational activity of these genes but also by the gating of channels and pumps by their own activity as well as by a range of other physiological and biochemical signals (Pietak and Levin, 2018, Cervera et al, 2018, Pietak and Levin, 2017, Cervera et al, 2020a, Cervera et al, 2019, Cervera et al, 2020b.…”

Section: Discussionmentioning

confidence: 99%

Precise control of ion channel and gap junction expression is required for patterning of the regenerating axolotl limb

Sousounis¹,

Erdoğan²,

Levin³

et al. 2020

Int. J. Dev. Biol.

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Axolotls and other salamanders have the capacity to regenerate lost tissue after an amputation or injury. Growth and morphogenesis are coordinated within cell groups in many contexts by the interplay of transcriptional networks and biophysical properties such as ion flows and voltage gradients. It is not, however, known whether regulators of a cell’s ionic state are involved in limb patterning at later stages of regeneration. Here we manipulated expression and activities of ion channels and gap junctions in vivo, in axolotl limb blastema cells. Limb amputations followed by retroviral infections were performed to drive expression of a human gap junction protein Connexin 26 (Cx26), potassium (Kir2.1-Y242F and Kv1.5) and sodium (NeoNav1.5) ion channel proteins along with EGFP control. Skeletal preparation revealed that overexpressing Cx26 caused syndactyly, while overexpression of ion channel proteins resulted in digit loss and structural abnormalities compared to EGFP expressing control limbs. Additionally, we showed that exposing limbs to the gap junction inhibitor lindane during the regeneration process caused digit loss. Our data reveal that manipulating native ion channel and gap junction function in blastema cells results in patterning defects involving the number and structure of the regenerated digits. Gap junctions and ion channels have been shown to mediate ion flows that control the endogenous voltage gradients which are tightly associated with the regulation of gene expression, cell cycle progression, migration, and other cellular behaviors. Therefore, we postulate that mis-expression of these channels may have disturbed this regulation causing uncoordinated cell behavior which results in morphological defects.

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“…Cells communicate electrically to sense anatomical states at long range [56], and use electric circuits to organize into networks that produce voltage prepatterns guiding gene expression and morphogenesis [57]. Research is now ongoing to refine computational models of information processing by non-neural bioelectric networks [58][59][60][61][62][63][64], which are becoming accurate enough that they can suggest interventions that repair complex birth defects such as brain mispatterning [65]. Moreover, elegant synthetic biology work such as that from Adam Cohen's group has begun to implement bioelectric circuits in minimal artificial tissue models [66][67][68].…”

Section: Tissue Decision-making: An Evolutionary Perspective On Anatomentioning

confidence: 99%

“…Indeed, the basic phenomenon of head/tail regeneration reveals that it is not a local, cell-level decision because the two wounds produced by bisection of a normal worm have radically different anatomical outcomes (head from one wound, tail from the other) despite the fact that the cells were immediately adjacent neighbours before the cut and thus were at the same positional information level along the axis. Thus, proper regeneration in the normal case, as in the modified scenarios described above, requires cells to communicate across significant distances to determine what structures exist, and which must be made anew [62,81,85,86].…”

Section: Hypothesis: Bistability In Memory Systemsmentioning

confidence: 99%

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration

Pezzulo

LaPalme

Durant

et al. 2021

Phil. Trans. R. Soc. B

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Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states—in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo . This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

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Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions

Cited by 14 publications

References 33 publications

Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds

Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds

Precise control of ion channel and gap junction expression is required for patterning of the regenerating axolotl limb

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration

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