Planarian regeneration as a model of anatomical homeostasis: Recent progress in biophysical and computational approaches

Abstract

Planarian behavior, physiology, and pattern control offer profound lessons for regenerative medicine, evolutionary biology, morphogenetic engineering, robotics, and unconventional computation. Despite recent advances in the molecular genetics of stem cell differentiation, this model organism's remarkable anatomical homeostasis provokes us with truly fundamental puzzles about the origin of large-scale shape and its relationship to the genome. In this review article, we first highlight several deep mysteries about planarian regeneration in the context of the current paradigm in this field. We then review recent progress in understanding of the physiological control of an endogenous, bioelectric pattern memory that guides regeneration, and how modulating this memory can permanently alter the flatworm's target morphology. Finally, we focus on computational approaches that complement reductive pathway analysis with synthetic, systems-level understanding of morphological decision-making. We analyze existing models of planarian pattern control and highlight recent successes and remaining knowledge gaps in this interdisciplinary frontier field.

The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation

“…Moreover, this is one illustration of the fact that the bioelectric pattern is not an epiphenomenon reflecting current tissue state, but an information structure that will determine (drive the outcome of) future regenerative events. We are currently modeling the state space of bioelectric circuits upstream of morphogen gradients in planaria to identify “edge of chaos” effects in which very similar starting conditions can drive fragments to end up in highly distinct regions of the planarian anatomical morphospace …”

Towards High-Throughput Chemobehavioural Phenomics in Neuropsychiatric Drug Discovery

“…They are best known from their phenomenal regeneration potential where even one adult planarian pluripotent stem cell (neoblast) can regenerate an entire functional organism [94,95,96]. This regenerative potential leads them to be fundamental models for regenerative medicine and healing research along with developmental and stem cell biology (Figure 6) [91,97].…”

Regenerative Adaptation to Electrochemical Perturbation in Planaria: A Molecular Analysis of Physiological Plasticity

“…Planarians are a class of free-living flatworms that contains many highly regenerative members (Cebrià et al., 2018, Saló et al., 2009). The freshwater planarian Dugesia japonica is one such species, able to restore an entire body (including the brain) from a mere fragment, scaling the growth with exquisite precision and ceasing further growth and remodeling when an allometrically correct body plan is complete (Levin et al., 2019, Sahu et al., 2017, Saló et al., 2009). Planarians possess bilateral symmetry, stem cell populations (Hill and Petersen, 2015, Tanaka and Reddien, 2011), and a true centralized brain with numerous complex behavioral responses including learning (Sarnat and Netsky, 1985, Corning and Freed, 1968).…”