Induction and the Turing-Child field in development

Abstract

The central problem in biological development is the understanding of epigenesis. The dominant theory of development in the last 80 years that also purports to explain epigenesis is induction theory. It suggests that development is driven by sequential inductions where each "induction" (in one sense of the word induction) is effected by the action of an inducing part of the embryo on a responding part of the embryo. The theory stems from Spemann and Mangold (W.Roux' Arch.f.Entw.d.Organis.u.mikrosk.Anat.100 (1924) 599) who transplanted a tissue from the dorsal blastopore lip of Triturus into the ventral ectoderm of another gastrula and thus initiated and "induced" (in another sense of the word induction) gastrulation and embryogenesis in the ventral side of the host that became a double embryo (siamese twins). We explain this induction, i.e. the formation of the double embryo, according to the Child theory and the Turing-Gierer-Meinhardt theory when it is also assumed that cAMP and ATP are the Turing activator and inhibitor, respectively. Spemann and Mangold (W.Roux' Arch.f.Entw.d.Organis.u.mikrosk.Anat.100 (1924) 599) also suggested that the ingressing mesoderm induces the overlying ectoderm to form the neural plate and neural tube. This 'neural induction', the 'primary embryonic induction', became the cornerstone of induction theory, i.e. of the sequential induction concept referred to above. But we argue that the metabolic gradients that precede and accompany neurulation, as obtained by Child, also for Triturus, arise through a Turing self-organization if it is assumed that cAMP and ATP are the Turing morphogens, and these gradients are the cause and primary event of neurulation. Thus there is no need to invoke the 'neural induction'. It is argued that fundamental events such as gastrulation and also organ formation are caused by the Turing-Child field and not by sequential induction. Similar principles, such as bud formation caused by a radial metabolic pattern that transforms to a longitudinal pattern, govern the formation, for example, of the mouth and the gut. The formation and localization of bottle cells is explained according to the Child-Turing field and modern biochemistry. The chemical metabolic pre-pattern precedes, and causes, morphogenesis and differentiation as envisaged by Turing. The Spemann and Mangold (W.Roux' Arch.f.Entw.d.Organis.u.mikrosk.Anat.100 (1924) 599) transplantation experiment when performed on a sea urchin duplicates not only the phenotype but also the metabolic (reduction) pattern. These experimental results, by Horstadius, predicted by Child, follow from the Turing-Gierer-Meinhardt theory if it is assumed that cAMP and ATP are the Turing morphogens. If the transplantation is performed not onto the whole sea urchin but onto only a part of it, that manifests only a part of the metabolic pattern, then from the part a phenotypic whole underlain by a normal and a whole metabolic pattern can be rescued. These experimental results of Horstadius follow from Turing theory if cAMP and ATP...

Morphogenetic fields in embryogenesis, regeneration, and cancer: Non-local control of complex patterning

“…With the discovery of the Hox code, it is well-accepted that gradients of Hox proteins specify a genetic prepattern for many areas, including the head (Hunt and Krumlauf, 1991), limb (Graham, 1994), and gut (Pitera et al, 1999). As presaged by Child (Child, 1941a), modern quantitative models of self-organization (Turing-type lateral inhibition/local activation systems) have been proposed (Meinhardt and Gierer, 1974; Schiffmann, 1997, 2001, 2004, 2005, 2006, 2011; Turing, 1990) to explain the origin and properties of the physiological pattern that usually precedes a spatially isomorphic anatomy. Recent data however have shown that true bioelectrical properties (voltage gradients) may also function as such templates of shape.…”

Where have the organizers gone? – The growth control system as a foundation of physiology

“…[12] Where are the organizers after embryogenesis? In embryogenesis, organizers are at the extreme points of curvature on the body surface [40]or interior interface such as the locally most convex (e.g., apical ectodermal ridge and other growth tips), concave or saddle points (e.g., zone of polarizing activity). [58] , [12] The growth control model suggests that organizers continue to exist at the extreme points of curvature at the surface of body or the interface of internal organs.…”

“…[64] Another common feature shared by organizer and acupuncture is that both of them have been shown to have higher metabolic rate than surrounding tissue. [40,[65][66][67][68] Both have also been shown to be associated with cAMP and Akt kinase: A gradient of cAMP and phosphorylated Akt kinase exists around organizers [40] while acupuncture can regulate cAMP [69] and Akt kinase. [70] Although the therapeutic effect of certain specific acupuncture point such as PC 6 has been established on randomized controlled trials, 67, 68 the existence of some acupuncture M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT points has been questioned due to the mixed results in acupuncture clinical trials when standardized acupuncture were compared with sham acupuncture at non-acupoints.…”

“…This has received increasing confirmation since the 1980s: Morphogens such as retinoic acid, Wnt, bone morphogenetic protein and Hedgehog as well as some organizers continue to exist and function after embryogenesis. [24][25][26][27][28] , [29,30] , [31] , [3,4,32,33] Many neurohumoral messengers such as serotonin, γ-aminobutyric acid, endorphins, angiotensin, adenosine, cAMP as well as cmyc, c-fos and other proto-oncogenes originate as morphogens, growth control messengers or regulators in embryogenesis [34] , [35] , [36] , [37] , [38,39] , [40] and continue to play important roles in adult physiology and pathophysiology.…”

Self-organization of developing embryo using scale-invariant approach

“…Ungrin et al reported a similar finding in the morphogenesis of hESCs cultured in suspension, which yielded embryoid bodies [16] with the property of self-organization. At later developmental stages such as organogenesis, Schiffmann reported self-organization in driving gastrulation and organ formation [17], where the increase in the mass of the organ and its cell number reportedly contribute to organogenesis [18]. Moreover, in vitro organogenesis showed a mechanism similar to that in vivo [19].…”