A phase-shift model for the spatial and temporal organization of developing systems

Brian C. Goodwin, Morrel H. Cohen

Research output: Contribution to journalArticle

208 Scopus citations

Abstract

The structure of any differentiated tissue results from a well-defined sequence of events in which the spatial and temporal organization of the developing tissue mass are intimately related. It is as though every cell has access to, and can read, a clock and a map (Wolpert's positional information). A model developed in the present paper is one in which the map arises from wave-like propagation of activity from localized clocks or pacemakers. Individual cells are supposed temporally organized in the sense that biochemical events essential for the control of development recur periodically. This temporal organization of an individual cell is converted by functional coupling between cells into a spatial ordering of the temporal organization. More explicitly a periodic event is postulated which propagates outward from a pacemaker region, synchronizing the tissue and providing a time base for development. Intercellular signalling, entrainment of all cells in the tissue by the fastest cells in the pacemaker region, and a refractory period to guarantee unidirectional propagation are the essential features of the propagation; they permit the derivation of a wave equation and a set of boundary conditions. An underlying gradient of frequency of the event establishes the position of the pacemaker region and the sense of propagation. A second event which propagates more slowly than the first provides positional information in the form of a one-dimensional sequence of surfaces of constant phase difference between the two events. A third event is used to regulate the pattern of phase difference and thus establish size-independent structures. The longest trajectory orthogonal to the surfaces of constant phase difference beginning at the pacemaker region and terminating at the regulating region defines a developmental axis of definite polarity. The model is readily extended to more than one axis, i.e. multi-dimensional positional information. It has a high informational capacity and is readily applied to the discussion of particular developmental phenomena. To illustrate its utility, we discuss development and regeneration in Hydra, positional in the early amphibian embryo, and the retinal-neural tectal projection of the amphibian visual system. Specific experiments to test for the existence of the postulated periodic events and their consequences are suggested. Some preliminary experimental results on Hydra tending to confirm the model are reported. Possible detailed realizations of the model in terms of, biochemical control circuits within the cell, are conjectured and discussed to show that the formal features of the model can be realized by well-recognized biochemical processes.

Original languageEnglish (US)
Pages (from-to)49-107
Number of pages59
JournalJournal of Theoretical Biology
Volume25
Issue number1
DOIs
StatePublished - Oct 1969
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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