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Biologists at Tufts University have developed a computational model of planarian (flatworm) regeneration that explains how fragments of planaria determine which end should form a tail and which should form a head. The development begins to answer an important question in regeneration research—what are the signals that determine the rebuilding of specific anatomical structures? Combining modeling and experiment, the researchers determined that the direction of nerve fibers sets the redistribution of chemical signals establishing the direction of the head-to-tail axis. The model was also able to predict the outcomes of numerous genetic, pharmacological, and surgical manipulations, such as worms with two heads or two tails.
The results published in the journal PLOS Computational Biology go beyond planaria, showing how computational modeling of physiological and genetic signals can help understand and control regeneration. The discovery that neural directionality helps guide organ-level structure could have many applications in biomedical contexts, such as regeneration in mammals, birth defects, bioengineering of organoids, and cancer.
Model - Simulation - Platform - Interface - Modeling
The computational model, using a new open-source simulation platform called the Planarian Interface for Modeling Body Organization (PLIMBO), incorporates many biological mechanisms driving regeneration—some published previously, and others discovered in the current study. This computational environment creates a realistic quantitative simulation of events taking place at the molecular, cellular, tissue, and whole organism levels. The model helped identify the important role neurons play in regeneration by providing active transport of morphogens—the molecules that help guide the growth and organization of cells into different tissues and anatomical structures. The researchers found that neurons played a critical role in reconstructing the polarity of the body plan (head to tail), as well as ensuring that morphogens could be rapidly distributed to enable the regeneration process to work effectively at different scales—from tiny fragments to complete bodies.
The model is basically a 2-dimensional map of a planarian...
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