John Tyler Bonner

Acrasin, acrasinase, and the sensitivity to acrasin in Dictyostelium discoideum☆☆☆

Abstract The purpose of this study was to examine the role in normal development of an acrasin (cyclic-AMP) and of an acrasinase (phophodiesterase) and the sensitivity to acrasin in the cellular slime mold Dictyostelium discoideum. Phosphodiesterase is secreted throughout the vegetative, aggregation, and migration stages. It is unclear whether or not cyclic-AMP is produced by vegetative amoebae, but there is a 100-fold increase between the beginning of aggregation and late aggregation, falling to a lower level during migration. The sensitivity to cyclic-AMP also increases 100-fold during aggregation, therefore the chemotactic system is at least 104 times more effective during aggregation than during the vegetative stage. Artificial patterns of amoebae may be produced by making an uneven distribution of cyclic-AMP in the agar with an even distribution of amoebae, or the reverse. The results of these experiments show: (1) the importance of phosphodiesterase in making steep gradients (and providing the basis of various acrasin assays), (2) the role of steep gradients of cyclic-AMP in producing cell adhesiveness, and possibly inhibiting centers; (3) the center-inducing capacity of a high concentration of externally applied cyclic-AMP. It is postulated that prior to normal aggregation, the distribution of chemicals affecting aggregation is homogeneous, and that this equilibrium is upset by sudden excessive sensitivity to cyclic-AMP and its production by certain cells, and the prevention of neighboring cells from having such an increase. The result, by chemotaxis, is an uneven distribution of cells which ultimately reach a new steady state in which they are massed together in groups spaced nonrandomly over the surface of the substratum.

Size and cycle : an essay on the structure of biology

For some years I have been concerned about the problem of the rela tion of genetics, evolutio , and evelopment. It has always seemed that their conventional relation is to some extent static and contrived, while in fact they must be closely integrated and part of one scheme. A problem with so many interrelated facets can be looked at a number of different ways, and here one will be chosen which it is hoped will help to reveal some of the fundamental relations. The method holds no dispute with any of the basic tenets of modern biology; this is not an attack on either the facts or the theories of biology today. Rather it is a regrouping of those facts and theories in such a fashion that new and deeper insights may possibly be achieved. Part of our present difficulty is that so many of our ways of looking at biology have slowly grown out of the past that we are infiltrated and imprisoned by a massive tangle of traditions and conventions. What we teach today is part biology and part history. There is nothing wrong with this but we do not always know where one begins and the other ends. The view taken here is that the life cycle is the central unit in biology. The notion of the organism is used in this sense, rather than that of an individual at a moment in time, such as the adult at maturity. Evolution then becomes the alteration of life cycles through time; genetics the inheritance mechanisms between cycles, and development all the changes in structure that take place during one life cycle. When looked at this way the size of the organism in the cycle takes on a particular significance. Size is correlated with time, for in general large organisms have long cycles and furthermore the different parts of the cycle can be readily classified on the basis of their size characteristics. The life cycle is a summation of all the molecular or biochemical steps, one following another in a well-ordered sequence. The difference between two cycles is a difference in the nature of the steps. They differ in their structure, their composition, and therefore the life cycle is a qualitative unit. A change in size of the organism, on the other hand, does not necessarily require that there be a qualitative difference in the steps, but merely more steps. Therefore the life cycle is quality, and size is quan tity. One is a statement of composition of matter and the changes in that composition; the other is merely a statement of quantity. Just as in

Induction of Stalk Cell Differentiation by Cyclic AMP in the Cellular Slime Mold Dictyostelium discoideum

Cyclic AMP, which is a cell attractant (acrasin) for Dictyostelium discoideum, will cause isolated, unaggregated cells to turn directly into stalk cells containing thick celluloselike walls and large vacuoles. From previous work we know that in the cell mass, acrasin is produced solely in the region of stalk formation during fruiting, that stalk formation involves a high level of catabolism, and that cyclic AMP stimulates catabolic enzymes in other systems. These facts obviously suggest that in the development of D. discoideum, cyclic AMP might be a key factor in stalk cell differentiation.

Perspective: the size-complexity rule.

Abstract It is widely accepted that bigger entities have a greater division of labor than smaller ones and this is reflected in the fact that larger multicellular organisms have a corresponding increase in the number of their cell types. This rule is examined in some detail from very small organisms to large animals, and plants, and societies. Compared to other size‐related rules, the size‐complexity rule is relatively rough and approximate, yet clearly it holds throughout the whole range of living organisms, as well as for societies. The relationship between size and complexity is analyzed by examining the effects of size increase and decrease: size increase requires an increase in complexity, whereas size decrease permits, and sometimes requires, a decrease in complexity. Conversely, an increase or decrease in complexity permits, but does not require changes in size. An especially compelling argument for the close relation between size and complexity can be found in size quorum sensing in very small multicellular organisms.

Studies on the Mechanics of Growth in the Common Mushroom, Agaricus Campestris

(1956). Studies on the Mechanics of Growth in the Common Mushroom, Agaricus Campestris. Mycologia: Vol. 48, No. 1, pp. 13-19.

Synthesis of cyclic AMP and phosphodiesterase in various species of cellular slime molds and its bearing on chemotaxis and differentiation

Abstract With 3 different chemotaxis tests it has been shown that of the 7 species of cellular slime molds examined in this study 4 are attracted strongly to cyclic AMP, while the remaining 3 show no chemotactic response whatsoever. Nevertheless it could be demonstrated that all the species produced extracellular cyclic AMP (although the nonresponders did produce less). All 7 species also synthesized a phosphodiesterase capable of converting cyclic AMP to 5′ AMP. Despite the fact that these substances are ubiquitous, there is strong evidence from Francis (1965) to support the hypothesis that the species that do not respond to cyclic AMP have a different acrasin that is essential for their aggregation. This raises the question of the function of cyclic AMP in these 3 species, and it is suggested that it may be involved in differentiation.

On the origin of differentiation.

Following the origin of multicellularity in many groups of primitive organisms there evolved more than one cell type. It has been assumed that this early differentiation is related to size — the larger the organism the more cell types. Here two very different kinds of organisms are considered: the volvocine algae that become multicellular by growth, and the cellular slime moulds that become multicellular by aggregation. In both cases there are species that have only one cell type and others that have two. It has been possible to show that there is a perfect correlation with size: the forms with two cell types are significantly larger than those with one. Also in both groups there are forms of intermediate size that will vary from one to two cell types depending on the size of the individuals, suggesting a form of quorum sensing. These observations reinforce the view that size plays a critical role in influencing the degree of differentiation.

Evidence for gas-induced orientation in the cellular slime molds☆

Abstract Evidence is presented to support the hypothesis that culminating slime molds orient with respect to their environment by producing a gas to which they are sensitive and they orient away from regions of high concentration (negative chemotaxis). A number of observations are described to show the capabilities and the sensitivity of the orienting mechanism, but as preliminary attempts to identify the gas were unsuccessful, its existence remains hypothetical.

OBSERVATIONS ON POLARITY IN THE SLIME MOLD DICTYOSTELIUM DISCOIDEUM

Experiments designed to give some insight into the nature of polarity were performed on the amoeboid slime mold Dictyostelium discoideum. The separate myxamoebae which stream together to form aggregations of myxamoebae show an external polarity and the resulting cell mass has a clear over-all antero-posteriority. In both cases it was shown that the internal parts do not reflect the external polarity. It is known from previous experiments that the aggregating myxamoebae orient in a concentration gradient of a chemical substance tentatively called acrasin, and that acrasin is found in later stages of development. By reversing the gradient of acrasin, separate myxamoebae did not back up but re-oriented towards the point of high concentration. However, it was shown by various experiments that the external acrasin gradient cannot always determine the direction of the polarity, for in the cell masses the polar movement occurs when there is no external gradient of acrasin, or in some cases away from the region o...

A new approach to the problem of aggregation in the cellular slime molds.

1. It has been shown that there is a substance (or substances) given off by the cellular slime mold amoebae that both orients aggregating cells ( e. g. in the Shaffer test) and increases the rate of movement of the cells. A simple, quantitative assay has been developed to test the rate of cell movement. Using both types of test in conjunction, we have been able to show that the substance(s) is produced before the aggregation of the amoebae and is even present in large amounts in the food source, E. coli.2. The substance(s) is not species-specific; it induces adhesiveness in cells approaching aggregation; it does not affect center formation or center inhibition (territory size); nor is it related to the phenomenon of cell repulsion.3. It is quite possible that there are many substances involved and the rate-increasing substance (s) is separate from orientation substance(s). Another possibility is that they are all one substance, which has hitherto been called acrasin. If this is the case then aggregation c...