Phenomenological aspects
One of the most striking characteristics of all developmental systems is a tendency to produce a normal end result in spite of injuries or abnormalities that may have affected the system in earlier stages. In many cases, perhaps in most, only injuries inflicted during a certain restricted period of development can be fully compensated for. During such periods the system is said to be capable of regulation or the restoration of normality.
Developmental regulation is often discussed in terms of homeostasis, or regulatory mechanisms. Many systems, including biological ones, exhibit a tendency to return to initial equilibrium once they are diverted from it. A developing system is, by definition, always changing in time, moving along some defined time trajectory, from an initial stage, such as a fertilized egg, through various larval stages to adulthood, and finally to senescence. The regulation that occurs in such systems is a regulation not back to an initial stable equilibrium, as in homeostasis, but to some future stretch of the time trajectory. The appropriate word to describe this process is homeorhesis, which means the restoration of a flow.
A second major phenomenological characteristic of development is that the end state attained is not unitary but can be analyzed into a number of different organs and tissues. The overall time trajectory of this system can, therefore, also be analyzed into a number of component trajectories, each leading to one or another of the end products that can be distinguished in the later stages. A major discovery of the early experiments on developing systems was that, in many cases at least, the different time trajectories diverge from one another relatively suddenly during some short period of development, which usually occurs well before any visible signs of divergence can be seen microscopically or by any other available means of analysis. The most dramatic and influential example of this was provided by studies on the development of the amphibian egg at the time of gastrulation, or formation of a hollow ball of cells. At this time the lower hemisphere of the embryo will be pushed inward (invaginated) to develop into the mesoderm and endoderm, and the upper hemisphere will remain on the surface, expanding in area to cover the whole embryo. Approximately one-third of the upper hemisphere will develop into the nervous system and the remainder into the skin. During the period when these morphogenetic movements of invagination and expansion are occurring, a process takes place by which a portion of the upper hemisphere enters a trajectory toward neural tissue and another part enters a trajectory leading to epidermal development. This process of determination of developmental pathways happens relatively quickly, during a period when the cells of the two different regions appear superficially alike. The occurrence of the determination can in fact be demonstrated only experimentally. Before it occurs, any part of the hemisphere can develop either into neural tissure or into skin. After it has happened, each part can develop only into one or the other of these alternatives.
It is clear that an adequate theory of development has to account not only for the processes by which a developing system moves along its appropriate time trajectory, but also for the nature of the processes by which the trajectories diverge from one another and become fixed or determined in the developing cells.
The determined state can be transmitted through many cell generations. An example of this transmission can be seen in Drosophila flies. The imaginal buds of Drosophila are small packets of cells that become separated from the main body of the embryo in the early stages of development. They persist throughout larval life and then enter into the differentiation of adult characteristics when stimulated to do so by the hormones secreted at the time of pupation. These pupation hormones disappear from the body of the adult insect, and imaginal buds transplanted into the body cavity of an adult undergo many cell generations, but they do not show any signs of differentiating into the specific tissues of the corresponding adult organ. After many generations of proliferation, however, the cells can be transplanted back into a larva ready to pupate; they thus submit to the pupation hormones and differentiation occurs. Through many generations of proliferation the cells have retained the determination as to which adult organ they will develop into when the pupation hormones become available.
Attempts to identify the determining agent have not yet been successful. Experiments on amphibian eggs, however, have given rise to one important general conclusion; namely, that the process of determination can take place only during a certain period of development, in which the cells of the upper half of the amphibian egg are poised between the two alternatives of development into neural tissue or into skin. They are said at this time to be “competent” for one or the other of these types of development. While they are in this state, and only while they are in it, a variety of external agents can switch them into one or the other of the possible pathways. Such a situation may be contrasted with one in which the cells were neutral, or featureless, and required then an external agent to transmit to them the quality of becoming nervous tissue or of becoming skin. This would mean that the reacting cells required information or instructions to be added to them from outside. Such a situation is not characteristic of biological development. Both in highly developed organisms such as amphibians and in simpler ones such as bacteria, the external agents act only as a releaser that switches on one or another process for which all of the necessary information is already incorporated in the cells concerned.