An hypothesis: phosphorylation fields as the source of positional information and cell differentiation--(cAMP, ATP) as the universal morphogenetic Turing couple

Abstract

It is hypothesized that (cAMP, ATP) is the elusive, universal Turing morphogenetic couple, which defies the second law of thermodynamics, i.e. the inexorable march towards homogeneity. cAMP and ATP can be distributed nonhomogeneously because the whole of the intermediary metabolism is so organized that they mutually satisfy the Turing bifurcation conditions upon nonlocalized application of an extracellular ligand, in particular a soluble peptide growth factor, which is nature's distinguished universal bifurcation parameter, acting homogeneously in space and removing the substrate inhibition from adenylate cyclase and thus triggering embryonic induction by triggering the (cAMP, ATP) Turing system. The hypothesis predicts that although the extracellular signal, the growth factor, is applied homogeneously, an organized "dissipative structure" will emerge spontaneously in the responding tissue; this "symmetry breaking" in a reaction-diffusion system occurs precisely in the manner envisaged by Turing, where (cAMP, ATP) constitutes the "reaction-diffusion system". This Turing bifurcation explicates the recent experiments where a differentiated embryoid emerges from the mere immersion of frog animal caps in an homogeneous growth factor solution, and similar experiments on chicks. The "metabolic" patterns found by Child and colleagues also reflect dissipative structures arising in a (cAMP, ATP) reaction-diffusion system when interpreted in the light of modern biochemistry: in particular, the localized glycogen depletion reflects localized cAMP; localized redox, respiratory or susceptibility activity reflects localized ATP. The dramatic collapse of organized structure found by Child and colleagues, for example, when Planaria or a section of it is exposed to an homogeneous environment of a narcotic solution, and the reemergence of structure upon return to water, are explained on the basis of the violation or satisfaction of the Turing bifurcation conditions with respect to (cAMP, ATP), respectively. cAMP is the "activator", ATP is the "inhibitor", and together they mutually satisfy the four activator-inhibitor inequalities, including the all-important autocatalytic cAMP production, as well as the lateral inhibition condition. The functional significance of gap junctions is to generate a multicellular purely reaction-diffusion system for (cAMP, ATP) as envisaged by Turing. It is emphasized that localization and pattern formation occur intracellularly in gap junction-coupled cells and not, as often suggested, extracellularly, the latter localization being too fragile to be maintained for long enough, and soon succumbing to the mixing effect of convection and movement. The activator-inhibitor property of (cAMP, ATP) means that the spatial distribution of cAMP and ATP could be not only nonhomogeneous but also of the same shape.(ABSTRACT TRUNCATED AT 400 WORDS)