The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis.

Complex living agents consist of cells, which are themselves competent sub-agents navigating physiological and metabolic spaces. Behaviour science, evolutionary developmental biology and the field of machine intelligence all seek to understand the scaling of biological cognition: what enables individual cells to integrate their activities to result in the emergence of a novel, higher-level intelligence with large-scale goals and competencies that belong to it and not to its parts? Here, we report the results of simulations based on the TAME framework, which proposes that evolution pivoted the collective intelligence of cells during morphogenesis of the body into traditional behavioural intelligence by scaling up homeostatic competencies of cells in metabolic space. In this article, we created a minimal in silico system (two-dimensional neural cellular automata) and tested the hypothesis that evolutionary dynamics are sufficient for low-level setpoints of metabolic homeostasis in individual cells to scale up to tissue-level emergent behaviour. Our system showed the evolution of the much more complex setpoints of cell collectives (tissues) that solve a problem in morphospace: the organization of a body-wide positional information axis (the classic French flag problem in developmental biology). We found that these emergent morphogenetic agents exhibit a number of predicted features, including the use of stress propagation dynamics to achieve the target morphology as well as the ability to recover from perturbation (robustness) and long-term stability (even though neither of these was directly selected for). Moreover, we observed an unexpected behaviour of sudden remodelling long after the system stabilizes. We tested this prediction in a biological system-regenerating planaria-and observed a very similar phenomenon. We propose that this system is a first step towards a quantitative understanding of how evolution scales minimal goal-directed behaviour (homeostatic loops) into higher-level problem-solving agents in morphogenetic and other spaces.

Nervous system and tissue polarity dynamically adapt to new morphologies in planaria.

The coordination of tissue-level polarity with organism-level polarity is crucial in development, disease, and regeneration. Here, we characterize a new example of large-scale control of dynamic remodeling of body polarity. Exploiting the flexibility of the body plan in regenerating planarians, we used mirror duplication of the primary axis to show how established tissue-level polarity adapts to new organism-level polarity. Characterization of epithelial planar cell polarity revealed a remarkable reorientation of tissue polarity in double-headed planarians. This reorientation of cilia occurs even following irradiation-induced loss of all stem cells, suggesting independence of the polarity change from the formation of new cells. The presence of the two heads plays an important role in regulating the rate of change in overall polarity. We further present data that suggest that the nervous system itself adapts its polarity to match the new organismal anatomy as revealed by changes in nerve transport driving distinct regenerative outcomes. Thus, in planaria tissue-level polarity can dynamically reorient to match the organism-level anatomical configuration.

Regulation of axial and head patterning during planarian regeneration by a commensal bacterium.

Some animals, such as planaria, can regenerate complex anatomical structures in a process regulated by genetic and biophysical factors, but additional external inputs into regeneration remain to be uncovered. Microbial communities inhabiting metazoan organisms are important for metabolic, immune, and disease processes, but their instructive influence over host structures remains largely unexplored. Here, we show that Aquitalea sp. FJL05, an endogenous commensal bacterium of Dugesia japonica planarians, and one of the small molecules it produces, indole, can influence axial and head patterning during regeneration, leading to regeneration of permanently two-headed animals. Testing the impact of indole on planaria tissues via RNA sequencing, we find that indole alters the regenerative outcomes in planarians through changes in expression to patterning genes, including a downregulation of Wnt pathway genes. These data provide a unique example of the product of a commensal bacterium modulating transcription of patterning genes to affect the host's anatomical structure during regeneration.