Electrical control of morphogenesis in regenerating Dugesia tigrina. II. Potential gradient vs. current density as control factors

2012

PLoS Comput Biol

106

A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences—using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an engineering-like style for reviews of the molecular developmental biology of biomedically important model systems, significant fresh insights and quantitative computational models will be developed by new collaborations between biology and the information sciences.

Section: Planarian Experiments: the Current Datasetmentioning

confidence: 99%

Modeling Planarian Regeneration: A Primer for Reverse-Engineering the Worm

Lobo¹,

Beane²,

2012

PLoS Comput Biol

106

“…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 .…”

Section: Discussionmentioning

confidence: 99%

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

Ferenc

Macromolecular Bioscience

2018

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.

“…Anatomical polarity can be altered by bioelectric gradient dynamics, [47][48][49]. This is due to the spatial patterns of membrane polarization in planaria being important for regeneration; significant alteration can be expected to alter the patterning outcome [26,44].…”

Section: Discussionmentioning

confidence: 99%

Effects of Ivermectin exposure on regeneration ofD. dorotocephalaplanaria

Ferenc¹,

2017

Preprint

The ability of cells to communicate is essential during pattern formation, as they make decisions that drive growth and form. One mode of cellular signaling is via bioelectrical properties determined by the activity of ion channels. Several studies have shown a role for bioelectric signaling in planarian regeneration, but these have focused on D. japonica and S. mediterranea. It is not known how the alterations of ion channel activity would affect regeneration in other species of planaria. Here, we tested the effect of ivermectin (IVM), a chloride channel opener drug commonly used to combat heart worms, on regeneration in a new species of planaria: D. dorotocephala. Exposure to IVM during regeneration resulted in patterning abnormalities, such as bifurcated tails with partial heads, as well as delayed regeneration. By testing the effect of drugs that target resting potential on regenerative repair in novel model species, additional insight is gained on the comparative roles of ionic signaling across taxa.