As was pointed out earlier, morphogenesis refers to all those processes by which parts of a developing system come to have a definite shape or to occupy particular relative positions in space. It may be regarded as the architecture of development. Morphogenetic processes involve the movement of parts of the developing system from one place to another in space, and therefore involve the action of physical forces, in contrast to processes of differentiation (see below), which require only chemical operations. Although in practice the physical and chemical processes of development normally proceed in close connection, for purposes of discussion it is often convenient to make an artificial separation between them.
There is an enormous variety of different kinds of structures within living organisms. They occur at all levels of size, from an elephant’s trunk to organelles within a cell, visible only with the electron microscope. There is still no satisfactory classification of the great range of processes by which these structures are brought into being. The following paragraphs constitute a tentative categorization that seems appropriate for the present state of biological thought on this topic.
Morphogenesis by differential growth
After their initiation, the various organs and regions of an organism may increase in size at different rates. Such processes of differential growth will change the overall shape of the body in which they occur. Processes of this kind take place very commonly in animals, particularly in the later stages of development. They are of major importance in the morphogenesis of plants, where the overall shape of the plant, the shape of individual leaves, and so on, depends primarily on the rates of growth of such component elements as the stems, the lateral shoots, and the vein and intervein material in leaves. In both animals and plants, such growth processes are greatly influenced by a variety of hormones. It is probable that factors internal to individual cells also always play a role.
Although differential growth may produce striking alterations in the general shape of organisms, these effects should probably be considered as somewhat superficial, since they only modify a basic pattern laid down by other processes. In a plant, for instance, the fundamental pattern is determined by the arrangement of the lateral buds around the central growing stem; whether these buds then grow fast or slowly relative to the stem is a secondary matter, however striking its results may be.
Morphogenetic fields
Many fundamental processes of pattern formation (e.g., the arrangement of lateral buds in growing plants) occur within areas or three-dimensional masses of tissue that show no obvious indications of where the various elements in the pattern will arise until they actually appear. Such masses of tissue, in which a pattern appears, have been spoken of as “fields.” This word was originally used in the early years of the 20th century by German authors who suggested an analogy between biological morphogenetic fields and such physical entities as magnetic or electromagnetic fields. The biological field is a description, but not an explanation, of the way in which the developing system behaves. The system develops as though each cell or subunit within it possessed “positional information” that specifies its location within the field and a set of instructions that lays down the developmental behaviour appropriate to each position.
There have been several attempts to account for the nature of the positional information and of the corresponding instructions. The oldest and best known of these is the gradient hypothesis. In many fields there is some region that is in some way “dominant,” so that the field appears as though organized around it. It is suggested that this region has a high concentration of some substance or activity, which falls off in a graded way throughout the rest of the field. The main deficiency of the hypothesis is that no one has yet succeeded in identifying satisfactorily the variables distributed in the gradients. Attempts to suppose that they are gradients of metabolic activity have, on investigation, always run into difficulties that can only be solved by defining metabolic activity in terms that reduce the hypothesis to a circular one in which metabolic activity is defined as that which is distributed in the gradient.
Recently, a new suggestion has been advanced concerning position information. Most processes within cells normally involve negative feedback control systems. These systems have a tendency to oscillate, or fluctuate regularly. In fact, any aspect of cell metabolism may be basically oscillatory in character; the cycle of cell growth and division may be only one example of a much more widespread phenomenon. The substances involved in these oscillations are likely to include diffusible molecules capable of influencing the behaviour of nearby cells. It is easy to envisage the possibility that there might be localized regions with oscillations of higher frequency or greater amplitude that act as centres from which trains of waves are radiated in all directions. It has been suggested that positional information is specified in terms of differences in phase between two or more such trains of transmitted oscillations.
Certain types of field phenomenon may involve an amplification of stochastic (random) variations. In systems containing a number of substances, with certain suitable rates of reaction and diffusion, chance variation on either side of an initial condition of equilibrium may become amplified both in amplitude and in the area involved. In this way, the processes may give rise to a pattern of differentiated areas, distributed in arrangements that depend on the boundary conditions.
Morphogenesis by the self-assembly of units
Complex structures may arise from the interaction between units that have characteristics such that they can fit together in a certain way. This is particularly appropriate for morphogenesis at the simple level of molecules or cells. Units such as the atoms of carbon, hydrogen, oxygen, nitrogen, and so on, can assemble themselves into orderly molecular structures, and larger molecules, such as those of tropocollagen, or protein subunits in general, can assemble themselves into complexes whose structure is dependent on localized and directional intermolecular forces. It seems that such comparatively large entities as the units that come together to form the head structures of bacteriophages or bacterial flagella are capable of orderly self-assembly, but the chemical forces that give rise to the interunit bonds are still little understood.
Processes that fall into the same general category as self-assembly may occur within aggregates of cells. The units that self-assemble are the cells themselves. Interaction and aggregation may be allowed to occur in assemblages of cells of one or more different kinds. In such cases it is commonly found that the originally isolated cells tend to adhere to one another, at first more or less at random and independently of their character, but later they become rearranged into a number of regions consisting of cells of a single kind. When the cells in the initial collection differ in two different characteristics, for instance in species and organ of origin, the assortment in some cases brings together cells from the same organ, in other cases cells from the same species. Mixtures of chick and mouse cells, for instance, reassort themselves into groups derived from the same organ, whereas cells from two different species of amphibia sort out into groups from the same species more or less independently of organ type.
This morphogenetic process probably has only a restricted application to the formation of structures in normal development, in which only in a few tissues (e.g., the connective system) do cells ever pass through a free stage in which they are not in intimate contact with other cells, and cells of different origin do not normally become intermingled so as to call for processes of reassortment. To explain normal morphogenetic processes of plants and animals one must look to the results that can be produced by the differential behaviour of cells that remain in constant close contact with one another. Several authors have shown how striking morphogenetic changes could be produced within a mass of cells that remain in contact, but that undergo changes in the intensity of adhesion between neighbouring cells, in the area of surface in the proportion to cell volume, and so on.
Differentiation
Differentiation is simply the process of becoming different. If, in connection with biological development, morphogenesis is set aside as a component for separate consideration, there are two distinct types of differentiation. In the first type, a part of a developing system will change in character as time passes; for instance, a part of the mesoderm, starting as embryonic cells with little internal features, gradually develops striated myofilaments, and with a lapse of time develops into a fully formed muscle fibre. In the second type, space rather than time is involved; for instance, other cells within the same mass of embryonic mesoderm may start to lay down an external matrix around them and eventually develop into cartilage. In development, differentiation in time involves the production of the characteristic features of the adult tissues, and is referred to as histogenesis. Differentiation in space involves an initially similar (homogeneous) mass of tissue becoming separated into different regions and is referred to as regionalization.
Histogenesis involves the synthesis of a number of new protein species according to an appropriate timetable. The most easily characterized are those proteins formed in a relatively late stage of histogenesis, such as myosin and actin in muscle cells. The synthesis of proteins is under the control of genes, and the problem of histogenesis essentially reduces to that of the genetic mechanisms that direct protein synthesis.
Regionalization is concerned with the appearance of differences between various parts of what is at first a homogeneous, or nearly homogeneous, mass. It is a prelude to histogenesis, which then proceeds in various directions in the different regions so demarcated. The processes by which the different regions acquire distinct contrasting characteristics must be related to some of the processes discussed under morphogenesis. Unlike morphogenesis, regionalization need not involve any change in the overall spatial shape of the tissues undergoing it. Regionalization falls rather into the type of process for which field theories have been invoked.
