Essay on the Phenomenon of Differentiation of Cells

It should be obvious by this time that protoplasm is an extremely versatile material. Although it exhibits basic characteristics which are found universally, variations exist in its chemical and physical constitution. Were this not the case, all cells, tissues, and organisms would be exactly alike.

Cells and protoplasmic structures may become so organized as to perform, specialized task that other cells or structures do not perform. The process by means of which such specialization is achieved is termed differentiation.

The differentiation of cells is most clearly demonstrated by the changes which occur in embryonic tissues of plants and animals between the time they arise by division of a parent cell and the time when they become fully specialized.

The causal mechanism leading to differentiation is not entirely clear, although some insight has been gained. As one studies the development of complex organisms from the one-celled stage to the highly organized adult from consisting of possibly trillions of cells, each with its particular functional specialization, the entire spectrum of organizational levels is encountered.

Specialized cells appear which are associated together in the formation of specific organs, and finally, organ systems are coordinated in the organism. The term differentiation may be used in a very broad sense to cover this entire spectrum of activity, or it may be used in a number of more restricted senses. Many biologists refer to the specialization of cells from a condition of apparent morphological and functional uniformity to a specialized state as histological differentiation. This process involves the chemical and structural changes which take place at the intracellular, cellular, and tissue levels.

Simultaneously with histological specialization, certain regions of the embryo undergo differentiation, that is, gross tissue organization occurs. Many biologists refer to such changes as regional differentiation or simply regionalization. At the same time, various organs assume their particular forms, and finally, the entire embryo takes on a specific morphological appearance.-

Differentiation at this higher level of organization is called morphogenesis. The noted embryologist C.H. Waddington has referred to these three aspects of differentiation as differentiation in time, differentiation in space, and differentiation in shape.

The sense in which we introduced the concept of differentiation at the beginning of this section-the sense in which the term is used most often-relates more directly to histological differentiation than to regionalization or morphogenesis, it is primarily to this aspect of differentiation that the following remarks are related. Perhaps an analogy will serve ^{t0 clar}ify these processes, at least with regard to their significance.

In our society, we produce children who are destined to become specialized members of a complex social group. To certain age, they are much alike except in potentiality and environment. They all attend school and study the same subjects, and at least until they finish their early education, they are not much different from each other as far as society and their roles in its behalf are concerned. They are merely students.

Gradually, however, they are led into different fields of endeavor. By the time a given class of unspecialized twelve-year-old has reached the age of thirty, great diversification has taken place. One person is a physician, a teacher, still another electrician, and so on. In a metaphorical sense, such individuals are the “cells” of a societal organism, and their specialization parallels in certain ways that of cells which develop in an actual organism.

Furthermore, as is the case with their societal analogues, the factors which contribute to the ultimate fate of a given cell or its progeny are quite complex. It is entirely beyond the scope of this book to attempt a detailed account of the mechanics of differentiation in various organisms, but perhaps mention of experimental approaches to the problem and some of the factors that have been discovered will enlightening.

What are the factors which start a given cell toward differentiation instead of cycling back into active mitosis? Put in other terms, what shuts off mitosis and turns on differentiation? We cannot answer these questions fully, but perhaps we can suggest some interesting possibilities.

Generally speaking, there are two classes of factors which determine the fate of a given cell and its division products. Certain themselves-while others are extrinsic – they depend upon influences which are external to the cells. Let us consider these two classes of influencing factors in turn. As a cell or a group of cells becomes specialized in structure and function, regardless of the final differentiated state, there must be accompanying chemical changes.

In the main, these changes involve the elaboration of different structural and functional proteins. It should be apparent by this time that what a cell can do is a reflection of the particular protein composition of the cell that is, the type and arrangement of structural and enzymatic proteins that control the metabolism of the cell.

In view of this, the embryologist S. Spiegel man has called differentiation “the controlled production of different enzyme patterns”. In the light of these concepts, it would be tempting to view the DNA units as the sole and complete factors which initiate and control development.

Thus, the development of an organism would simply be the progressive unfolding and expression of the encoded information of the DNA complement as it directs the enzymatic patterns which lead to the final differentiated state. However, this is not the case. Since the multicellularity of the embryo results from repeated cell divisions, in which process the chromosomes containing the genes are simply equated in the new cells, it is reasonable to assume that all cells of the organism possess identical genetic complements.

The question then arises as to why every cell of the organism does not exhibit identical patterns of differentiation. Since they obviously do not, it seems reasonable if not essential to assume that there must be other intrinsic or extrinsic factors which play a part in the initiation and control of differentiation. The eggs of many species of animal’s showery distinct cytoplasm regions.

These visibly different regions are the result of a differential concentration of yolk, pigment, and other materials. Even in eggs which show no visible exists as a result of chemical differences in contrasting areas of the egg. Sea urchin eggs, discussed below exhibit such metabolic gradients.

There is a considerable amount of experimental evidence which indicates that as the fertilized egg of divides and a multicelluar complex is formed, the daughter nuclei may become located in diverse cytoplasm environments. Therefore, certain cytoplasm factors may initiate the Process of cell differentiation by acting upon the genetic material in different ways.

Thus, a differential genetic activity is initiated in cells of different regions. Perhaps we can visualize how “depressed” genes control the release of messenger RNA into the cytoplasm, where protein synthesis takes place.

The introduction of new protein molecules changes the molecular ecology of the particular cell, and if these proteins are absent in some contrasting cell, it is not difficult to see that subsequent events in differentiation will probably not be the same in the two cells.

Thus, a given cell may develop a complicated feedback system which leads to a particular channel of differentiation. In addition, it is possible to divide the sea urchin egg into animal and vegetal halves and fertilize each half, or to cause the first divisional plane of a fertilized egg to be shifted so as to divide the egg into an animal half and a vegetal half.

In neither case does normal development occur when the two halves are separated. It appears that a different distribution of cytoplasmic factors along the animal-vegetal gradient precludes development.

However, some animal embryos divide in such a way that a differential distribution is initiated at the first cleavage. Experimental studies indicate that extrinsic factors also play an important role in development.

Furthermore, chemical influences from one cell group to another are known to prevail. In a vertebrate embryo, groups of cells develop as “organizers”, and this is the first stage in different ion of cells to form specific organs. There organizers influence cells around them, which are as yet undifferentiated, to form certain tissues. That this influence is a chemical one is shown by the phenomenon that induction may be effected by the use of extracts from organizer cells.

For instance, the first organizer to form in the frog embryo is a certain patch of tissue which influences, among other things, the development of the nervous system. If cells of this organizer are transplanted to a portion of the embryo far removed from the normal site of nervous system development, they induce a nervous system there.

However, it is not necessary to transplant the cells themselves; if they are destroyed and extracts of their contents are injected just beneath the surface of an embryo at some point of its body, a nervous system will develop at that point.

In other words, such experiments as this indicate that substances from one cell group may pass into another cell group in the normal embryo with the result that the latter cells are influenced to differentiate along certain fines.

Thus, any such chemical substances constitute extrinsic factors as far as the influenced cells are concerned, even though they are not extrinsic to the embryo itself. Much is yet to be learned about the exact chemical basis for such influence, but organization and induction are very important factors in differentiation. Aside from the fundamental causes, or the how of cell differentiation, embryologists have gained much information about the actual processes, or the what, in several types of organisms. It has been common to use harmless dyes, graphite, or other such materials for making cells.

Similarly, methods for studying cellular differentiation have been developed with regard to plants. From such studies, a wealth of information has been gained regarding the ultimate fate of various embryonic plant and animal parts.

Thus far in our consideration of differentiation, we have thought largely it terms of histological specialization, that is, the development of cells to form a part of some tissue which is known by its particular function.

How can we account for the ability of unicellular organisms to exhibit within a single cell the many accomplishments necessary’ to the maintenance of life? It must be concluded that a cell such as

Amoeba is obliged to be a jack-of-all-trades in its activities, and any differentiation within its protoplasm is of necessity based on cytological specialization of cell organelles. A great deal of research has been directed toward the identification of structure with function in such organisms, and much evidence for a high degree of specialization has accumulated.

These activities may be restored if a nucleus from another amoeba is transplanted into the cell. It has been shown by centrifuging mitochondria from cells and testing them for physiological properties that they serve as storehouses for enzymes without which the cell could not carry on respiration.

Other organelles of the cell have been similarly shown to perform definite and specific functions. Actually, all cells exhibit a high degree of cytological differentiations, as is shown by the well-high universal appearance of nuclei, mitochondria, and certain other organelles.

The organization of an endoplasmic reticulum, which was previously noted, indicates a high degree of structural organization. It will be recalled that the sea urchin egg is organized in such a way as to require early divisions in a certain plane for normal development to occur.

Thus, it should not be thought that cells of multicellular organisms are specialized past all cytological differentiation; some, in fact, are hardly specialized all histological.

The unicellular forms are the Robinson Crusoes of the cell world, and cells such as nerve cells of higher animal bodies are the physicians, teachers, and electricians of a complex society. The physician is, nevertheless, obliged to retain certain unspecialized abilities to at least a degree; he can still drive a nail or change an automobile tire, although he is neither a carpenter nor a mechanic.

In the same way, even highly specialized cells retain some of their unspecialized abilities. Nerve cells are specialized in the conduction of impulses, but all cells are somewhat capable of this.

One of the many outstanding biological principles which have come to be recognized as a result of such cell studies as those described above is that unicellular organisms are no less complex than their multicellular superiors except in a purely organizational sense.

It is simply that their organization is completely cytological viewpoint toward the co-called simple organisms and has bred a profound respect for protoplasm and its complexities in all life.