The chemical nature of Organizers can only be well explained after we have examined the powerful influence exerted by chorda and mesoderm on neighboring tissues in an organism which was dramatically demonstrated in 1924 by the famous German embryologist Hans Spemann and his co-worker Otto Mangold. Their experiment, one of the landmarks in developmental biology, has profound implications. What they did was to take a small piece of tissue from the dorsal lip of a gastrula and transplant it into the ventral side of another gastrula. The result of this operation was that the ectoderm on the ventral side of the host invaginated to form a second ventrally placed neural tube. On sectioning the embryo, it was found that the other structures such as gut and mesodermal somites, consisting of mixed host and graft tissues, had also been found on the ventral side of the host. In some cases an almost complete secondary embryo was present.
In interpreting the result of Spemann and Mangold’s experiment it is important to appreciate the composition and fate of the dorsal lip. The dorsal slip is made up of cells which are mainly destined to become the notochord and mesodermal somites. As the distinction between these two types of cell is not very clear-cut, it is best to refer to the whole area as chorda-mesoderm. In the early gastrula the chorda-mesoderm lies immediately above the dorsal lip of the blastopore where invagination takes place. As gastrulation proceeds this area invaginates to form the roof of the archenteron. Once it has got into this position, and provided that certain other conditions are satisfied , it induces the overlying ectoderm to invaginate and form a neural tube.
The importance of Spemann and Mangold’s experiment is that it provides a vivid demonstration of the profound influence which one tissue can have on a neighboring tissue during development. Such tissues are called organizers and they are said to induce adjacent cells to develop in a particular way. The process by which one tissue influence another is called induction. A tissue which is capable of responding to the stimulus of an organizer is described as competent.
Powerful though it is, chorda-mesoderm is by no means the only organizer encountered during development. Most tissues are capable of exerting some degree of induction at some stage in their history. Typically the inductive power of an organizer changes as development proceeds, so that a tissue which has a strong influence in, say, the gastrula, may lose its inductive ability in later stages of development.
It is also true that a tissue which is readily induced by an adjacent organizer at one stage of development may become incapable of being induced at a later stage, i.e. it loses its competence. This applies, for example, to the neural plate. The period during which the ectoderm responds to the inductive influence of underlying chorda tissue is quite short. Once the neural tube has been formed, the ectoderm loses its capacity to respond and will only develop into epidermis.
So as development proceeds, the capacity of different tissues to induce or respond to changes increases considerably. The chorda-mesoderm is the first clearly demonstrable organizer encountered in the course of development, and it is responsible for determining the basic organization of the embryo. For this reason we call it the primary organizer. The primary organizer induces the formation of certain structures which in turn act as secondary organizers inducing the development of further structures, and so on. There is, as it were, a hierarchy or organizers (primary, secondary, tertiary etc.) each responsible of inducing the formation of certain structures in the embryo.
This hierarchical system would doubtless appear very complex if one were to consider the development of an entire organism with all its inter-related organ systems. However, the basic principles can be seen clearly if we confine ourselves to development of one organ, the eye. The development of the vertebrate eye is well understood, and the system of organizers controlling it has been analyzed in some detail. Let us see what happens.
As the eye is intimately associated with the brain, the first step in its development is the formation of the neural tube which, as we have already seen, is induced by the underlying notochord. The neural tube becomes the central nervous system which expands interiorly to form the brain. The next step is the development of a pouch-like evagination, the so-called optic vesicle, on each side of the forebrain. Later the optic vesicles invaginate to become cup-shaped, but in the meantime they induce the adjacent ectoderm to form the lens rudiment. The lens then acts as a further organizer, inducing the adjacent epidermis to develop into the cornea.
The precise sources of all the inductive influences required to produce a complete eye are still a matter of controversy, but one thing seems certain: it is the optic vesicle which is mainly responsible for formation of the lens. This has been shown by two experiments. In the first, the optic vesicle on one side of the brain is carefully removed without disturbing the epidermis immediately alongside it. The result is that a lens is not formed on that side of the head though, as would be expected, a normal eye develops on the other intact side.
The second experiment is spectacular if somewhat bizarre. The optic vesicle is removed from one side of the brain and a tiny slit is made in the epidermis further down the body, in the flank region for example. The optic vesicle is then push into this slit so that it comes to lie immediately beneath the epidermis. The epidermis itself suffers no undue damage as a result of this procedure; it quickly heals up after the optic vesicle has been implanted. Now normally the embryonic epidermis in this part of the body would give rise to the superficial layer of the skin, but under the influence of the optic vesicle it forms a lens, the end result is the formation of a structurally complete eye in the animal’s flank. This eye is described as atopic, meaning “in the wrong’. Such eyes have no innervations and are therefore non-functional as they cannot ‘see’.
THE CHEMICAL NATURE OF ORGANIZERS
In the light of such experiment it would be difficult to deny the validity of the organizer concept or the chemical nature of organizers. Even quite simple experiments indicate unequivocally that different tissues have a profound effect on each other, and the pattern of development is to a large extent molded by these influences. This being so, the question arises as to what chemical constituent or the chemical nature of organizers, is the effective agent in influencing neighboring cells. This question has been tackled by extracting the chemical components of organizers or better put, chemical nature of organizers (chorda-mesoderm for example) and testing their effects on other tissues. The organizer tissue is ground up, centrifuged and the chemical constituents separated and purified. Each constituent is then tested by placing it in contact with a tissue that is known to be competent. The effect of the particular chemical substance on the development of the tissue is then followed. What conclusion can be drawn from the results of these experiments? It would be nice to be able to say that such-and-such a chemical substance causes active cell differentiation, but unfortunately, at the present time, this is simply not possible. The results of the experiments which have been done so far are inconsistent. The anomalies are caused partly by inadequate isolation of the chemical substances, and consistent results are not likely to be forthcoming until the techniques of extraction and purification are improved. The results to date tend to favor protein as the most likely candidate though nucleic acid is claimed by some to be the active principle in organizers. What may eventually emerge is that induction is brought about by protein, the latter being synthesized in the cytoplasm under the influence of nucleic acid.
Cells may, of course, influence one another in less drastic ways than is involved in the transformation of one tissue into another. For example, the influence may simply be that the cells attract one another so as to hold the organism together. This is seen in the way isolated sponge cells come together after being separated, or the amoeboid cells of slime moulds, after leading a solitary existence, aggregate to form a multicellular reproductive body. In the slime mould Dictyostelium the aggregation, consisting of as many as 100, 000 cells, assumes a specific shape and moves as an integrated unit. Aggregation is caused by the amoeboid cells producing a substance which makes them orientate towards one another. Recently it has been shown that this substance is none other than cyclic Adenosine Monophosphate.