Optimal placement of multiple morphogen sources.
During development, cells grow, differentiate, divide, and die according to their spatial positions, yet the positional information given to cells by morphogens (diffusive chemicals) includes considerable noises from various origins. In this paper, we examine a relationship between fluctuations in morphogen concentrations that the cells receive and the precision of positional specification by the morphogens in multidimensional space. As a method to quantify the precision, we introduce a measure of "ambiguity of positional information," based on the information entropy. We discover that the location of morphogen sources crucially affects the ambiguity, and that the ambiguity becomes minimum when the angle made by gradient vectors of different morphogens cross at a right angle in a target region under a given organ geometry (orthogonality principle). We conjecture that morphogen sources in development might be placed at the nearly optimal position that minimizes the ambiguity of positional information. This is supported by experimental data on the configurations of two major sources of spatial patterning, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA), in vertebrate limb development. Indeed, their predicted configuration agrees very well with the one observed in experiments. We believe that the placement of morphogen sources to minimize the ambiguity of positional information is a basic principle in development of multicellular organisms beyond this particular example.
PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan.
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Morishita
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Iwasa
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D004475:Ectoderm / Q000378:metabolism*; D004627:Embryonic Induction; D019277:Entropy; D018878:Limb Buds / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics / Q000378:metabolism