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First published online October 23, 2009
doi: 10.1242/10.1242/dev.041764

Development 136, 3831-3840 (2009)
Published by The Company of Biologists 2009
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Algorithm of myogenic differentiation in higher-order organisms

Ron Piran1,*, Einat Halperin2,*, Noga Guttmann-Raviv2, Ehud Keinan1,3,{dagger} and Ram Reshef2,4,{dagger}

1 Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
2 Faculty of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
3 Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4 Department of Biology and Department of Evolutionary & Environmental Biology, The Faculty of Sciences and Science Education, Haifa University, Mount Carmel, Haifa, 31905, Israel.

{dagger} Authors for correspondence (keinan{at}tx.technion.ac.il; reshefr{at}tx.technion.ac.il)

Accepted 12 September 2009

Cell fate determination is governed by complex signaling molecules at appropriate concentrations that regulate the cell decision-making process. In vertebrates, however, concentration and kinetic parameters are practically unknown, and therefore the mechanism by which these molecules interact is obscure. In myogenesis, for example, multipotent cells differentiate into skeletal muscle as a result of appropriate interplay between several signaling molecules, which is not sufficiently characterized. Here we demonstrate that treatment of biochemical events with SAT (satisfiability) formalism, which has been primarily applied for solving decision-making problems, can provide a simple conceptual tool for describing the relationship between causes and effects in biological phenomena. Specifically, we applied the Lukasiewicz logic to a diffusible protein system that leads to myogenesis. The creation of an automaton that describes the myogenesis SAT problem has led to a comprehensive overview of this non-trivial phenomenon and also to a hypothesis that was subsequently verified experimentally. This example demonstrates the power of applying Lukasiewicz logic in describing and predicting any decision-making problem in general, and developmental processes in particular.

Key words: Finite automaton, Formal logic, Myogenesis, SAT problem, Somitogenesis, Chick


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