Cellular differentiation

“ In all such cases the definite number of cells in the entire body or in a particular organ must be determined by a definite number of cell divisions which proceed from the egg, or from the protoblast of the organ, and this limitation in the number of cell divisions must in some way be determined by heredity. Since increase of differentiation is associated with decrease of cell division, the latter being stopped altogether when differentiation has reached a certain stage, it seems probable that all cases of cell constancy are due to constancy of differentiation. ”

“ Many kinds of cells in higher animals perish as a result of their function; it is, so to speak, their business to perish, to break up; this is the case with many glandular and epithelial cells. It may very well be that, in many of the highly differentiated tissue-cells, such as nerve, muscle, and glandular cells, the high [Pg 263] differentiation in itself excludes the possibility of unlimited length of life and multiplication. ”

“ The difference between the two kinds of cells consists therefore in the much greater number, the much smaller size, and the greater activity of the male cells, and in the smaller number but much larger size of the female cells—a differentiation in accordance with the principle of division of labour, depending on the fact that the two kinds of cells must reach each other, and yet must contain a certain mass of living protoplasm. ”

“ In order that perfection of the adult structure should be attained, it is necessary that the mere undifferentiated cells, each with a small body of protoplasm, should acquire first an increased amount of protoplasm, and that then from the increased protoplasm should be taken the material to result in differentiation, in specialization.
An undifferentiated cell performs all the fundamental functions of life. An amœba, or any unicellular organism such as I have presented to you upon the screen, does everything which is indispensable to life. It takes food ”

“ But in any case, after this process of cell-division has proceeded for a certain time, differentiation begins to set in—some cells become modified in one way, others in another, and from what was a relatively homogeneous mass an organized embryo, with highly differentiated parts, appears. ”

“ Around each of these as a center the protoplasm of the mother cell is seen to have become differentiated in the form of a clear spherule, and we have thus corresponding to each of the new nuclei a young naked cell, which soon secretes over its surface a membrane of cellulose. The new cells, when once formed, multiply by division, press one on the other, and so combining into a cellular mass, constitute the completed endosperm. ”

“ But when an organism undergoes great changes of structure during development, the cells, which at each stage are supposed to be directly derived from previously existing cells, must likewise be greatly changed in nature; this change is attributed by the supporters of the cellular doctrine to some inherent power which the cells possess, and not to any external agency. Others maintain that cells and tissues of all kinds may be formed, independently of pre-existing cells, from plastic lymph or blastema. ”

“ The Division Period. Oogonia and Spermatogonia
When the primitive sex cells are first distinguishable they differ from other cells only in the fact that they are less differentiated; they have relatively larger nuclei and smaller cell bodies—a condition which is indicative of little differentiation of the cell body since the products of differentiation such as fibres, secretions, etc., swell the size of the cell body, but do not contribute to the growth of the nucleus. ”

“ It is also important to remember that a cell that has synthesized DNA is a cell that, with a few exceptions, will divide in the very near future. Thus, for an understanding of the mechanisms that control cellular proliferation, it is important to investigate the factors that control DNA synthesis. ”

“ As implied by these quotations, a constant and progressive differentiation of cells prevails in the developing embryo; and when complete, certain groups of cells act as specialists in doing only certain kinds of work for the body. These cells maintain their specific characters in a very remarkable degree under normal conditions. Under various abnormal conditions, however, these cells may become modified as to functions, so that cells or tissues of one type may assume more or less completely the characters of another type. ”

“ There are also workers who melt down outworn letters and still other workers who make new letters for further use; these are the enzymes, special kinds of proteins. If we wish to continue the analogy, we may say that each kind of cell in the organism has a different subeditor, who writes that cell’s own editorial. Actually we might say that all cells have the same board of editors in common, but only one editor functions in any given type of cell. In biological terms this means that only a portion of all the cellular DNA is active in each cell. ”

“ The nucleus is the essence of the cell. And the doctrine of cellular continuity emphasizes the fact that the nuclei of all the cells of the body are derived by a process of divisional growth from the first segmentation-nucleus which results from the union of the nuclei of the ovum and the sperm. In this sense, then, however late the germinal cells appear as such, they are in direct continuity with the germinal cell from which they, in common with all the cells of the organism, derive their origin. In this sense there is a true continuity of germ-cells. ”

“ We are thus brought back to the fundamental question as to how the germ-cells arise in the organism. Is it possible that the nucleoplasm of the germ-cell, with its immensely complex molecular structure, potentially containing all the specific peculiarities of an individual, can arise from the nucleoplasm of any of the body-cells,—a substance which, as we have just seen, has lost the power of originating any new kind of cell, because of the continual simplification of its structure during development? ”

“ There is always a tendency in development to throw back the differentiation of the embryonic cells into definite tissues to as late a date as possible. This takes place in order to enable the changes of form, which every organ undergoes, in repeating even in an abbreviated way its phylogenetic history, to be effected with the least expenditure of energy. ”

“ It is clear that at each successive stage the molecular structure of the nucleoplasm must be further removed from that of the germ-plasm, and that, at the same time, the cells of each successive stage must also diverge more widely among themselves in the molecular structure of their nucleoplasm. Early in development each cell must possess its own peculiar nucleoplasm, for the further course of development is peculiar to each cell. ”

“ The chromatin stands towards the other contents of the cell in the same relation that a nerve-element stands to any element of an organism which it excites." "We may infer that cell-evolution was, under one of its aspects, a change from a stage in which the exciting substance and the substance excited were mingled with approximate uniformity, to a stage in which the exciting substance was gathered together into the nucleus and finally into the chromosomes, leaving behind the substance excited, now distinguished as cytoplasm." ”

“ Every cell contains idioplasm, since every cell-nucleus contains chromatin, but I call the idioplasm of the germ-cells germ-plasm, or the primary-constituent-substance of the whole organism, and the complexes of primary constituents necessary to the production of a complete individual—whose presence we have just shown to be theoretically necessary—I call ids. In many cases these 'ids' might be synonymous with chromosomes, at least in all the cases in which the chromosomes are simple, that is, are not composed of several similarly formed structures. ”

“ Thus the suggestion arises that in the embryo a cellular lining is formed to a cœlomic cavity (mesothelium) composed of cells which have no communication with the nervous system, and are capable of a separate existence as free individuals, either in the form of germinal cells or of lymphocytes, hæmocytes, and plasma-cells, so that these latter free cells may be considered as living an independent existence in the body, and ministering to it in the same sense as the germ-cells live an independent existence in the body. ”

“ This same type of cell division, with equal division of the chromosomes and more or less unequal division of the cell body continues long after the cleavage stages—indeed throughout the entire period of embryonic development. Sometimes the division of the cell body is equal, the daughter cells being alike; sometimes it is unequal or differential— but always the division of the chromosomes is equal and non-differential. When once the various tissues have been differentiated the further divisions in these tissue cells are usually non-differential even in the case of the cell bodies. ”

“ The siliceous cell-wall is covered on the outside by a layer of protoplasm called the coleoderm. This layer may be quite thin and evident only when treated with fuchsin or Bismarck brown, or it may be of considerable thickness. The cell contains the cytoplasma, protoplasm, cell-sap, endochrome, pyrenoids, oil globules and nucleus, together with certain other less understood bodies. ”

“ He assumes that the primitive, original germplasm has a most complicated molecular structure, while the histogenous nuclearplasms for tissue-cells, like muscle-cells, nerve-cells, sense-cells, gland-cells, and so forth, have relatively simpler structures. As, during the growth of the embryo, the germplasm becomes transformed into the histogenous plasms, its molecular structure becomes simpler in proportion to the fewer different possibilities of development each separated portion of it comes to contain. ”

“ Here comparative research yields the important result that EVERY OVUM IS AT FIRST A SIMPLE CELL. I say this is very important, because our whole science of embryology now resolves itself into the problem: "How does the multicellular organism arise from the unicellular?" Every organic individual is at first a simple cell, and as such an elementary organism, or a unit of individuality. This cell produces a cluster of cells by segmentation, and from these develops the multicellular organism, or individual of higher rank. ”

“ If the appearance of the whole cell gives us any knowledge as to the structure of its nuclear idioplasm, we may be sure that the development of a primitive germ-cell proceeds without a break, from the moment of its first recognizable formation, to the ultimate production of distinct male or female sexual cells. ”

“ By the time the chick is ready to be hatched there are millions.
Usually, however, a cell is small—just as much protoplasm as its still more minute nucleus can keep going; though here, again, one must be guarded, for there may be several nuclei instead of only one. The protoplasm on the external surface and around the nucleus is specialized into a more or less definite membrane. To this outer envelope are attached fine fibrils, which join up to a small body within the cell, called the centrosome, and by the lengthening and shortening of these its shape can be altered. ”

“ Our recent knowledge of the cell cycle has therefore led to a shift in the focus of investigation from mitosis to DNA synthesis.
Another point to remember is that not all cells keep going through the cell cycle indefinitely. As shown in Figure 25, when a cell divides, the daughter cells have two alternatives, either to go through another cycle or to leave it altogether. Cells that leave the cycle are called differentiated cells and will eventually die without any further division. Many cells in an adult organism also have lost the capacity to make DNA and therefore the capacity to divide. ”

“ Thus it is just as inconceivable that either a homogeneous or a heterogeneous cell-colony possessing the physiological value of a multicellular individual should continue to grow to an unlimited extent by continued cell-division, as it is inconceivable that a unicellular being should increase in size to an unlimited extent. ”

“ This process clearly indicates very high specialization on the part of germ-cells. For we see by it that although these cells when young resemble all other cells in being capable of self-multiplication by binary division (thus reproducing cells exactly like themselves) , when older they lose this power ”

“ In some cases the protoplasm at the circumference is so modified as to give the appearance of a limiting membrane called the cell wall. In brief, then, a cell is a mass of nucleated protoplasm; the nucleus may have a nucleolus, and the cell may be limited by a cell wall. Every tissue of the human body is formed through the agency of protoplasmic cells, although in most cases the changes they undergo are so great that little evidence remains of their existence. ”

“ On the other hand, processes which lead to the increase of the general protoplasm in a cell, either by the growth of the protoplasm already present or by the conversion of metaplasm into protoplasm, lead also to the growth of the nucleus, to increased interchange between nucleus and protoplasm, and hence to increased powers of assimilation, cell division and regulation. Anything which decreases the interchange between nucleus and protoplasm leads to senility ”