The cell in development and inheritance (1900) 8

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Wilson EB. The Cell in Development and Inheritance. Second edition (1900) New York, 1900.

   Cell development and inheritance (1900): Introduction | List of Figures | Chapter I General Sketch of the Cell | Chapter II Cell-division | Chapter III The Germ-cells | Chapter IV Fertilization of the Ovum | Chapter V Reduction of the Chromosomes, Oogenesis and Spermatogenesis | Chapter VI Some Problems of Cell-organization | Chapter VII Some Aspects of Cell-chemistry and Cell-physiology | Chapter VIII Cell-division and Development | Chapter IX Theories of Inheritance and Development | Glossary
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Chapter VIII Cell-Division and Development

" Wir konnen demnach endlich den Satz aufstellen, dass sammtliche im entwickelten Zustandc vorhandenen Zellen oder Aequivalente von Zellen durch cine fortschreitende Gliedcrung der Eizclle in morphologisch ahnlichc Elemente entstehen, und dass die in einer emhryonischen Organ-Anlage enthaltenden Zellen, so gering auch ihre Zahl sein mag, dennoch die ausschlicssliche ungegliederte Anlage fiir sammtliche Formbestandtheile der spateren Organe enthalten."

Remak.

  • Untersuchungen, 1 855, p. 140.


Since the early work of Kolliker and Remak it has been recognized that the cleavage or segmentation of the ovum, with which the development of all higher animals begins, is nothing other than a rapid series of mitotic cell-divisions by which the egg splits up into the elements of the tissues. This process is merely a continuation of that by which the germ-cell arose in the parental body. A long pause, however, intervenes during the latter period of its ovarian life, during which no divisions take place. Throughout this period the egg leads, on the whole, a somewhat passive existence, devoting itself especially to the storage of potential energy to be used during the intense activity that is to come. Its power of division remains dormant until the period of full maturity approaches. The entrance of the spermatozoon arouses in the egg a new phase of activity. Its power of division, which may have lain dormant for months or years, is suddenly raised to the highest pitch of intensity, and in a very short time it gives rise by division to a myriad of descendants which are ultimately differentiated into the elements of the tissues.

The divisions of the egg during cleavage are exactly comparable with those of tissue-cells, and all of the essential phenomena of mitosis are of the same general character in both. But for two reasons the cleavage of the egg possesses a higher interest than any other case of cell-division. First, the egg-cell gives rise by division not only to cells like itself, as is the case with most tissue-cells, but also to many other kinds of cells. The operation of cleavage is therefore immediately connected with the process of differentiation, which is the most fundamental phenomenon in development. Second, definite relations may often be traced between the planes of division and the structural axes of the adult body, and these relations are sometimes so c'early marked and appear so early that with the very first cleavage the position in which tie embryo will finally appear in the egg may be exactly predicted. Such *• promorphological " relations of the segmenting egg possess a very high interest in their bearing on the theory of germinal localization and on account of the light which they throw on the conditions of the formative process.


The present chapter is in the main a prelude to that which follows, its purpose being to sketch some of the external features of early development regarded as particular expressions of the gen. cral rules of cell-division. For this purpose we may consider the cleavage of the ovum under two heads, namely : —

1. The Geometrical Relations of Cleavage-forms, with reference to the general rules of cell-division.

2. The Promorphological Relations of the blastomeres and cleavage-planes to the parts of the adult body to which they give rise.

A. Geometrical Relations of Cleavage-forms

The geometrical relations of the cleavage-planes and the relative size and position of the cells vary endlessly in detail, being modified bv innumerable mechanical and other conditions, such as the amount and distribution of the inert yolk or deutoplasm, the shape of the ovum as a whole, and the like. Yet all the forms of cleavage can be referred to a single type which has been moulded this way or that by special conditions, and which is itself an expression of two general rules of cell-division, first formulated by Sachs in the case of plantcells. These are : —

1. The cell typically tends to divide into equal parts.

2. Each new plane of division tends to intersect the preceding plane at a right angle.

In the simplest and least modified forms the direction of the cleavage-planes, and hence the general configuration of the cellsystem, depends on the general form of the dividing mass; for, as Sachs has shown, the cleavage-planes tend to be either vertical to the surface (anticlines) or parallel to it (periclines). Ideal schemes of division may thus be constructed for various geometrical figures. In a flat circular disc, for example, the anticlinal planes pass through the radii ; the periclines are circles concentric with the periphery. If the disc be elongated to form an ellipse, the periclines also become ellipses, while the anticlines are converted into hyperbolas confocal with the periclines. If it have the form of a parabola, the periclines and anticlines form two systems of confocal parabolas intersecting at right angles. All these schemes are mutatis mutandis, directly convertible into the corresponding solid forms in three dimensions.


Sachs has shown in the most beautiful manner that all the above ideal types are closely approximated in nature, and Rauber has applied the same principle to the cleavage of animal-cells. The discoid or spheroid form is more or less nearly realized in the thalloid growths of



Fig. 168. — Geometrical relations of cleavage-planes in gro' after various authors.]

A. Flat ellipsoidal germ-disc of Milottsia (Rosanoff) ; nearly typical relation of elliptic periclines and hyperbolic anticlines. B. C. Apical view of terminal knob on epidermal hair of PiHguitda. B. shows the ellipsoid type. C. the circular (spherical type), somewhat modified [only anticlines present). D. Growing point of Satvinia (Pringsheim), typical ellipsoid type; the single pericline is, however, incomplete. E. Growing point of Atolla (Strasburger) ; circular or spheroidal type transitional 10 ellipsoidal. F. Root-cap of Eguisetum (Nageli and Lritgeb) ; modified circular type. G. Cross-section ol leaf-vein. Triekemami (Prantl) : ellipsoidal type with incomplete periclines. H. Embryo of Aliima; typical ellipsoid type, pericline incomplete only at lower side. /. Growing point ol bud of the pine (Aiits) ; typical paraboloid type, both anticlines and periclines having the form of parabolas (Sachs).


various lower plants, in the embryos of flowering plants, and elsewhere (Fig. 168). The paraboloid form is according to Sachs characteristic of the growing points of many higher plants ; and here, too, the actual form is remarkably similar to the ideal scheme (Fig. 168, 1).


For our purpose the most important form is the sphere, which is the typical shape of the egg-cell; and all forms of cleavage may be related to the typical division of a sphere in accordance with Sachs's rules. The ideal form of cleavage would here be a succession of rectangular cleavages in the three dimensions of space, the anticlines passing through the centre so as to split the egg in the initial stages successively into halves, quadrants, and octants, the periclines being parallel to the surface so as to separate the inner ends of these cells from the outer. No case is known in which this order is accurately followed throughout, and the periclinal cleavages are of comparatively rare occurrence, being found as a regular feature of the early cleavage only in those cases where the primary germ-layers are separated by delamination. The simplest and clearest form of eggcleavage occurs in eggs like those of echinoderms, which are of spherical form, and in which the deutoplasm is small in amount and equally distributed through its substance. Such a cleavage is beautifully displayed in the egg of the holothurian Synapta, as shown in the diagrams, Fig. 169, constructed from Selenka's drawings. The first cleavage is vertical, or meridional, passing through the egg-axis and dividing the egg into equal halves. The second, which is also meridional, cuts the first plane at right angles and divides the egg into quadrants. The third is horizontal, or equatorial, dividing the egg into equal octants. The order of division is thus far exactly that demanded by Sachs's rule and agrees precisely with the cleavage of various kinds of spherical plant-cells. The later cleavages depart from the ideal type in the absence of periclinal divisions, the embryo becoming hollow, and its walls consisting of a single layer of cells in which anticlinal cleavages occur in regular rectangular succession. The fourth cleavage is again meridional, giving two tiers of eight cells each ; the fifth is horizontal, dividing each tier into an upper and a lower layer. The regular alternation is continued up to the ninth division (giving 512 cells), when the divisions pause while the gastrulation begins. In later stages the regularity is lost.

Hertwigs Development of Sachs's Rules. — Beside Sachs's rules may be placed two others formulated by Oscar Hertwig in 1884, which bear directly on the facts just outlined and which lie behind Sachs's principle of the rectangular intersection of successive divisionplanes. These are : —

1 . The nucleus tends to take up a position at the centre of its sphere of influence y i.e. of the protoplasmic mass in zuhich it lies.

2. The axis of the mitotic fgu res typically lies in the longest axis of the protoplasmic mass, and division therefore tends to cut this axis at a right angle.

The second rule explains the normal succession of the division planes according to Sachs's second rule. The first division of a homogeneous spherical egg, for example, is followed by a second division at right angles to it, since each hemisphere is twice as long in the plane of division as in any plane vertical to it. The mitotic figure of the second division lies therefore parallel to the first plane, which forms the base of the hemisphere, and the ensuing division is vertical to it. The same applies to the third division, since each quadrant is as long as the entire egg while at most only half its diameter. Division is therefore transverse to the long axis and vertical to the first two planes.

Taken together the rules of Sachs and Hertwig, applied to the egg, give us a kind of ideal type or model, well illustrated by the



Pig. 169. — Cleavage of Ibe ovum in Ihe hololhurian Synapta (slightly tchematized). [After Selenka.]

A-E. Successive cleavages (o the 33-cell stage. F. Blastula of laS cells.

cleavage of Synapta, described above, to which all the forms of cleavage may conveniently be referred as a basis of comparison. Numerous exceptions to all four of these rules are, however, known, and they are of little value save as a starting-point for a closer study of the facts. Cleavage of such schematic regularity as that of Synapta is extremely rare, both the form and the order of division being endlessly varied and in extreme cases showing scarcely a discoverable connection with the "type." We may conveniently consider these modifications under the following three heads: —


366 CEU^DIVISION AXD DEVELOPMENT

1. Variation in the rhythm of division.

2. Displacement of the cells (including variations in the direction of cleavage).

3. Unequal division of the cells.

Nothing is more common than a departure from the regular rhythm of division. The variations are sometimes quite irregular, sometimes follow a definite rule, as, for instance, in the annelid Xercis (Fig. 171), where the typical succession in the number of cells is with great constancy 2, 4, 8, 16, 20, 23, 29, 32, 37, 38, 41, 42, after which the order is more or less variable. The factors that determine such variations in the rhythm of division are very little understood. Balfour, one of the first to consider the subject, sought an explanation in the varying distribution of metaplasmic substances, maintaining ('75,

8o) that the rapidity of division in any part of the ovum is in general inversely proportional to the amount of deutoplasm that it contains. The entire inadequacy of this view has been demonstrated by a long series of precise studies on cell-lineage, which show that while the large deutoplasm-bearing cells often do divide more slowly than the smaller protoplasmic ones the reverse is often the case, while remarkable differences in the rhythm of division are often observed in cells which do not perceptibly differ in metaplasmic content. 1 All the evidence indicates that the rhythm of division is at bottom determined by factors of a very complex character which cannot be disentangled from those which control growth in general. Lillie ('95, '99) points out the very interesting fact, determined through an analysis of the cell-lineage of mollusks and annelids, that the rate of cleavage shows a direct relation to the period at which the products become functional. Thus in Unio the more rapid cleavage of a certain large cell ("d. 2 M ), formed at the fourth cleavage, is obviously correlated with the early formation of the shell-gland to which it gives rise, while the relatively slow rate of division in the first ectomerequartet is correlated with reduction of the pne-trochal region. The prospective character shown here will be found to apply also to other characters of cleavage, as described beyond.

When we turn to the factors that determine the direction of cleavage or the displacement of cells subsequent to division, we find, as in the case of the division-rhythm, obvious mechanical factors combined with others far more complex. The arrangement of tissue-cells usually tends toward that of least resistance or greatest economy of space ; and in this regard they have been shown to conform, broadly speaking, with the behaviour of elastic spheres, such as soap-bubbles when massed together and free to move. Such bodies, as Plateau

1 Cf. Wilson, '92, Kofoid, '94, Lillie, '95, Zur Strassen, '95, Ziegler, '95, and especially Jennings, '97.


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS


367


and Lamarle have shown, assume a polyhedral form and tend toward such an arrangement that the area of surface-contact between them is a minimum. Spheres in a mass thus tend to assume the form of interlocking polyhedrons so arranged that three planes intersect in a line, while four lines and six planes meet at a point. If arranged in a single layer on an extended surface, they assume the form of



C D

Fig. 170. — Cleavage of Polygordius, from life.

A. Four-cell stage, from above. B. Corresponding view of eight-cell stage, the same (contrast Fig. 169, C) . D. Sixteen-cell stage from the side.


C. Side view of


hexagonal prisms, three planes meeting along a line as before. Both these forms are commonly shown in the arrangement of the cells of plant and animal tissues; and Berthold ('86) and Errera ('86, '87), carefully analyzing the phenomena, have endeavoured to show that not only the form and relative position of cells, but also the direction of cell-division, is, partially at least, thus determined.

It is through displacements of the cells of this type that many of


368 CELL-DIVISION AND DEVELOPMENT

the most frequent modifications of cleavage arise. Sometimes, as in Synapta, the alternation of the cells is effected through displacement of the blastomeres after their formation. More commonly it arises during the division of the cells, and may even be predetermined by the position of the mitotic figures before the slightest external sign of division. Thus arises that form of cleavage known as the spiral, oblique, or alternating type, where the blastomeres interlock during their formation and lie in the position of least resistance from the beginning. This form of cleavage, especially characteristic of many worms and mollusks, is typically shown by the egg of Polygordins (Fig. 170). The four-celled stage is nearly like that of Synapta, though even here the cells slightly interlock. The third division is, however, oblique, the four upper cells being virtually rotated to the right (with the hands of a watch) so as to alternate with the four lower ones. The fourth cleavage is likewise oblique, but at right angles to the third, so that all of the cells interlock as shown in Fig. 170, D. This alternation regularly recurs for a considerable period.

In many worms and mollusks the obliquity of cleavage appears still earlier, at the second cleavage, the four cells being so arranged that two of them meet along a " cross-furrow " at the lower pole of the egg, while the other two meet at the upper pole along a similar, though often shorter, cross-furrow at right angles to the lower {e.g. in Nereis, Fig. 171). It is a curious fact that the direction of the displacement is quite constant, the first or upper quartet in the eightcell stage being rotated to the right, or with the hands of a watch, the second quartet to the left, the third to the right, and so on. Crampton ('94) has discovered the remarkable fact that in Pfiysa, a gasteropod having a reversed or sinistral shell, the whole order of displacement is likewise reversed, and the same has recently been shown by Holmes ('99) to be true of Ancylus.

The spiral or alternating type of cleavage beautifully illustrates Sachs's second rule as affected by modifying conditions ; for, as may be seen by an inspection of Figs. 170, 171, each division-plane is approximately at right angles to the preceding and succeeding (whence the " alternation of the spirals " described by students of cell-lineage), while they are so directed that each cell as it is formed is placed at once in the position of least resistance in the mass, i.e. in the position of minimal surface-contact. It is impossible to resist the conclusion that one of the factors by which the position of the cells (and hence the direction of cell-division) is determined is a purely mechanical one, identical with that which determines the arrangement of soap-bubbles and the like.

Very little acquaintance with the facts of development is however


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS 369

required to show- that this purely mechanical factor, though doubtless real, must be subordinate to some other. This is strikingly shown, for example, in the development of annelids and mollusks, where the spiral cleavage, strictly maintained during the earlier stages, finally gives way more or less completely to a bilateral type of division in which the rule of minimal surface-contact is often violated. We see here a tendency operating directly against, and finally overcoming,



Pig. 171. — Cleavage of Ntr. nd of a marked determinate ch


£ F

An example of a spiral cleavage, unequal from the beginning

A. Two-cell stage (the circles are oil-drops). B, Four-cell stage; the second cleavage-plane passes through the future median plane. C. The same from the right side. D. Eight-cell stage. E, Sixteen cells ; from the cells marked / arises the prototroch or larval ciliated belt, from X the ventral nerve-cord and other structures, from D the mcsoblast-bnnds, the germ-cells, and a part ol the alimentary canal. F. Twenty-nine-cell stage, from the right side ; f. girdle of protolrochal cells which give rise to the ciliated belt

the mechanical factor which predominates in the earlier stages; and in some cases, e.g. in the egg of Claveliita (Fig. 177) and other tunicates, this tendency predominates from the beginning. In both these cases this " tendency " is obviously related to the growth-process to which the future bilateral embryo will owe its form ; x and every attempt to explain the position of the cells and the direction of cleavage must reckon with the morphogenic process taken as a whole. The blastomere is not merely a cell dividing under the stress of rude 1 Cf. WiUon ('9* p. 444)


370


CELL-DIVISION AND DEVELOPMENT


mechanical conditions; it is beyond this "a builder which lays one stone here, another there, each of which is placed with reference to future development." 1

The third class of modifications, due to unequal division of the cells, not only leads to the most extreme types of cleavage but also to its



C D

Fig. 172. — The eight-cell stage of four different animals showing gradations in the inequality of the third cleavage.

A. The leech Clepune (Whitman). B. The chsctopod Rhynckelmis (Vejdovsky). C. The lamellibranch Unio (Lillie). D. Amphioxus,


most difficult problems. Unequal divisions appear sooner or later in all forms of cleavage, the perfect equality so long maintained in Synapta being a rare phenomenon. The period at which the inequality first appears varies greatly in different forms. In Polygordius (Fig. 170) the first marked inequality appears at the fifth cleavage;

1 Lillie, '95, p. 46.


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS 371

in sea-urchins it appears at the fourth (Fig. 3); in Amphioxus at the third (Fig. 172); in the tunicate Clavelina at the second (Fig. 177); in Nereis at the first division (Figs. 60, 171). The extent of the inequality varies in like manner. Taking the third cleavage as a type, we may trace every transition from an equal division (echinoderms, Polygordius), through forms in which it is but slightly marked {Amphioxus, frog), those in which it is conspicuous {Nereis, Lymnaa, polyclades, Pctromyzon, etc.), to forms such as Clepsine, where the cells of the upper quartet are so minute as to appear like mere buds from the four large lower cells (Fig. 172). At the extreme of the series we reach the partial or meroblastic cleavage, such as occurs in the cephalopods, in many fishes, and in birds and reptiles. Here the lower hemisphere of the egg does not divide at all, or only at a late period, segmentation being confined to a disc-like region or blastoderm at one pole of the egg (Fig. 173).

Very interesting is the case of the tcloblasts or pole-cells characteristic of the development of many annelids and mollusks and found in some arthropods. These remarkable cells are large blastomeres, set aside early in the development, which bud forth smaller cells in regular succession at a fixed point, thus giving rise to long cords of cells (Fig. 175). The teloblasts are especially characteristic of apical growth, such as occurs in the elongation of the body in annelids, and they are closely analogous to the apical cells situated at the growing point in many plants, such as the ferns and stoneworts.

Still more suggestive is the formation of rudimentary cells, arising as minute buds from the larger blastomeres, and, in some cases, apparently taking no part in the formation of the embryo (Fig. 174). 1

We are as far removed from an explanation of unequal division as from that of the rhythm and direction of division. Inequality of division, like difference of rhythm, is often correlated with inequalities in the distribution of metaplasmic substances — a fact generalized by Balfour in the statement ('8o) that the size of the cells formed in cleavage varies inversely to the relative amount of protoplasm in the % region of the egg from which they arise. Thus, in all telolecithal ova, where the deutoplasm is mainly stored in the lower or vegetative hemisphere, as in many worms, mollusks, and vertebrates, the cells of the upper or protoplasmic hemisphere are smaller than those of the lower, and may be distinguished as micromeres from the larger macromeres of the lower hemisphere. The size-ratio between micromeres and macromeres is on the whole directly proportional to the ratio between protoplasm and deutoplasm. Partial or discoidal cleavage occurs when the mass of deutoplasm is so great as entirely to prevent cleavage in the lower hemisphere. This has been beautifully con 1 Sec Wilson, '98, '99, 2.


372


CEtl-DIF/SION AND DEVELOPMENT


firmed by O. Hertwig ('98), who, by placing frogs' eggs in a centrifugal machine, has caused them to undergo a meroblastic cleavage through the artificial accumulation of yolk at the lower pole, due to the centrifugal force.

While doubtless containing an element of truth, this explanation is, however, no more adequate than Balfour's rule regarding the relation between deutoplasm and rhythm (p. 366); for innumerable cases are known in which no correlation can be made out between the distribution of inert substance and the inequality of division. This is the case, for example, with the teloblasts mentioned above, which contain no deutoplasm, yet regularly divide unequally. It seems to be inap


Fig. 173.


the squid Loligo. [Watase.)


plicable to the inequalities of the first two divisions in annelids and gastcropods. It is conspicuously inadequate in the history of individual blastomeres, where the history of division has been accurately determined. In Nereis, for example, a large cell known as the first somatoblast, formed at the fourth cleavage (A', Fig. 171, E\ undergoes an invariable order of division, three unequal divisions being followed by an equal one, then by three other unequal divisions, and again by an equal. This cell contains little or no deutoplasm and undergoes no perceptible changes of substance.

The collapse of the rule is most complete in case of the rudimentary cells referred to above. In some of the annelids, eg. in Aricia, where they were first observed,' these cells are derived from the very large primary mcsoblast-cell, which first divides into equal halves. Each of these then buds forth a cell so small as to be no larger than a polar body, and then immediately proceeds to give rise

1 Cf. Wilson, 'ga, 'oS.


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS


373


to the mesoblast-bands by continued divisions, always in the same plane at right angles to that in which the rudimentary cells are formed (Fig. 174)- The cause of the definite succession of equal and unequal divisions is here wholly unexplained. No less difficult is the extreme inequality of division involved in the formation of the polar bodies. We cannot explain this through the fact that deutoplasm is collected in the lower hemisphere ; for, on the one hand, the succeeding divisions (first cleavages) are often equal, while, on the other hand, the inequality is no less pronounced in eggs having equally



Pig. 174-— Rudimentary blastomcres in the embryo of an annelid, Aritia. A. From lower pole; rudimentary cells Mr.*; the heavy outline is the lip of ihe blastopore. B. The same in sagittal optical section, showing rudimentary cell (f). primary mesoblasl f,W), and mesoblast-band («).

distributed deutoplasm, or in those, like cchinoderm-eggs, which are " alecithal."

Such cases prove that Balfour's law is only a partial explanation, being probably the expression of a more deeply lying cause, and there is reason to believe that this cause lies outside the immediate mechanism of mitosis. Conklin ('94) has called attention to the fact 1 that the immediate cause of the inequality probably does not lie either in the nucleus or in the amphiaster ; for not only the chromatin-halvcs, but also the asters, are exactly equal in the early prophases, and the inequality of the asters only appears as the division proceeds. Probably, therefore, the cause lies in some relation between the mitotic figure and the cell-body in which it lies. 1 In the cleavage of gasteropod eggs.


CELL-DIVISION AA'D DEVELOPMENT


I believe there is reason to accept the conclusion that this relation is one of position, however caused. A central position of the mitotic



figure results in an equal division ; an eccentric position caused by a radial movement of the mitotic figure, in the direction of its axis toward the periphery, leads to unequal division, and the greater the


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS 375

eccentricity, the greater the inequality, an extreme form being beautifully shown in the formation of the polar bodies. Here the original amphiaster is perfectly symmetrical, with the asters of equal size (Fig. 97, A). As the spindle rotates into its radial position and approaches the periphery, the development of the outer aster becomes, as it were, suppressed, while the central aster becomes enormously large. The size of the aster, in other words, depends upon the extent of the cytoplasmic area that falls within the sphere of influence of the ccntrosome ; and this area depends upon the position of the centrosome. If, therefore, the polar amphiaster could be artificially prevented from moving to its peripheral position, the egg would probably divide equally. 1

This leads us to a further consideration of the attempts that have been made to explain the movements of the mitotic figure through mechanical or other causes. 2 Highly interesting experiments have been made by Pfliiger ('84), Roux ('85), Dricsch ('92), and a number of later investigators which show that the direction of cleavage may be determined, or at least modified, by such a purely mechanical cause as pressure, through which the form of the dividing mass is changed.

Thus, Driesch has shown that when the eggs of sea-urchins are flattened by pressure, the amphiasters all assume the position of least resistance, i.e. parallel to the flattened sides, so that the cleavages are all vertical, and the egg segments as a flat plate of eight, sixteen, or thirty-two cells (Fig. 186). This is totally different from the normal form of cleavage; yet such eggs, when released from pressure, are capable of development and give rise to normal embryos. This interesting experiment makes it highly probable that the disc-like cleavage of meroblastic eggs, like that of the squid or bird, is in some degree a mechanical result of the accumulation of yolk by which the formative protoplasmic region of the ovum is reduced to a thin layer at the upper pole ; and it indicates, further, that the unequal cleavage of less modified telolecithal eggs, like those of the frog or snail, are in like manner due to the displacement of the mitotic figures toward the upper pole.

The results of Pfliiger's and Driesch's pressure experiments obviously harmonize with Hertwig's second rule, for the position of least resistance for the spindle is obviously in the long axis of the protoplasmic mass which is here artificially modified ; and it harmonizes further with Driiner's hypothesis of the active elongation of the spindle in mitosis (p. 105). There are, however, a large number of facts which show that neither the form of the protoplasmic mass nor

1 Cf. Francotte on the polar bodies of Turbellaria, p. 235.

2 For a good review and critique, see Jennings, '97.


376 CELL-DIVISIOX AXD DEVELOPMENT

the distribution of metaplasmic materials is sufficient to explain the position of the spindle, whether with reference to the direction or the inequality of the cleavage.

As regards the direction of the spindle, Berthold ('86) long since clearly pointed out that prismatic or cylindrical vegetable cells, for instance, those of the cambium, often divide lengthwise ; and numerous contradictions of Hertwig's " law " have since been observed by students of cell-lineage with such accuracy that all attempts to explain them away have failed. 1 In some of these cases the position of the spindle is not that of least but of greatest resistance,* the spindle ac


[KOSTANECKI and SlEDLECK].]


tually pushing away the adjoining cell to make way for itself. Similar difficulties, some of which have been already considered (p. 372), stand in the way of the attempt to explain the eccentricity of the spindle in unequal division. All these considerations drive us to the view that the simpler mechanical factors, such as pressure, form, and the like, are subordinate to far more subtle and complex operations involved in the genera! development of the organism, a conclusion strikingly illustrated by the phenomena of teloblastic division (p. 371 ), where the constant succession of unequal divisions, always in the

1 Cf. Watase ('91), Mead ('94, '97, 2), Heidenhain ("95), Wheeler ('95), Castle ('96), Jennings C'J7'h

1 See especially the case observed by Mead ("94, '97, a), in the egg of Amphitriie.


GEOMETRICAL RELATIONS OF CLEAVAGE-FORMS 377

same plane, is correlated with a deeply lying law of growth affecting the entire formation of the body. We cannot comprehend the forms of cleavage without reference to the end-result ; and thus these phenomena acquire a certain teleological character so happily expressed by Lillie (p. 370). This has been clearly recognized in various ways by a number of recent writers. Roux ('94), while seeking to explain many of the operations of mitosis on a mechanical basis, holds that the position of the spindle is partly determined by "immanent" nuclear tendencies. Braem ('94) recognizes that the position of the spindle is determined not merely as that of least resistance for the mitotic figure, but also for that of the resulting products. I pointed out ('92) that the bilateral form of cleavage in annelids must be regarded as a " forerunner " of the adult bilaterality. Jennings ('97) concludes that the form and direction of cleavage are related to the later morphogenetic processes ; and many similar expressions occur in the works of recent students of cell-lineage. 1

The clearest and best expression of this view is, however, given by Lillie ('95, '99), who not only correlates the direction and rate of cleavage, but also the size-relations of the cleavage-cells with the arrangement of the adult parts, pointing out that in general the size, as well as the position, of the blastomeres is directly correlated with that of the parts to which they give rise, and showing that on this basis "one can thus go over every detail of the cleavage, and knowing the fate of the cells, can explain all the irregularities and peculiarities exhibited." 2 Of the justice of this conclusion I think any one must be thoroughly convinced who carefully examines the recent literature of cell-lineage. It gives no real explanation of the phenomena, and is hardly more than a restatement of fact. Neither does it in any way lessen the importance of studying fully the mechanical conditions of cell-division. It does, however, show how inadequate have been most of the attempts thus far to formulate the " laws " of cell-division, and how superficially the subject has been considered by some of those who have sought for such "laws."

We now pass naturally to the second or promorphological aspect of cleavage, to a study of which we are driven by the foregoing considerations.

1 Conklin ('99) believes that many of the peculiarities of cleavage may be explained by the assumption of protoplasmic currents which " carry the centrosomes where they will, and control the direction of division and the relative size and quality of the daughter-cells,' , I.e., p. 90. He suggests that such currents are of a chemotropic character, but recognizes that their causation and direction remain unexplained.

1 Cf. ('95), P- 39


378 CELL-DIVISION AND DEVELOPMENT


B. Promorphological Relations of Cleavage

The cleavage of the ovum has thus far been considered in the main as a problem of cell-division. We have now to regard it in an even more interesting and suggestive aspect ; namely, in its morphological relations to the body to which it gives rise. From what has been said above it is evident that cleavage is not merely a process by which the egg simply splits up into indifferent cells which, to use the phrase of Pfliiger, have no more definite relation to the structure of the adult body than have snowflakes to the avalanche to which they contribute. 1 It is a remarkable fact that in a very large number of cases a precise relation exists between the cleavage-products and the adult parts to which they give rise ; and this relation may often be traced back to the beginning of development, so that from the first division onward we are able to predict the exact future of every individual cell. In this regard the cleavage of the ovum often goes forward with a wonderful clocklike precision, giving the impression of a strictly ordered scries in which every division plays a definite role and has a fixed relation to all that precedes and follows it.

But more than this, the apparent predetermination of the embryo may often be traced still farther back to the regions of the undivided and even unfertilized ovum. The egg, therefore, may exhibit a distinct promorphology ; and the morphological aspect of cleavage must be considered in relation to the promorphology of the ovum of which it is an expression. ..

I . Promorphology of the Ovum

(a) Polarity and the Egg-axis. — It was long ago recognized by von Baer ('34) tnat * ne unsegmented egg of the frog has a definite egg-axis connecting two differentiated poles, and that the position of the embryo is definitely related to it. The great embryologist pointed out, further, that the early cleavage-planes also are definitely related to it, the first two passing through it in two meridians intersecting each other at a right angle, while the third is transverse to it, and is hence equatorial. 2 Remak afterward recognized the fact 3 that the larger cells of the lower hemisphere represent, broadly speaking, the "vegetative layer" of von Baer, i.e. the inner germ-layer or entoblast, from which the alimentary organs arise ; while the smaller cells

i C8 3 \ p. 64.

2 The third plane is in this case not precisely at the equator, but considerably above it, forming a " parallel " cleavage.

8 '55» P* I 3°* Among others who early laid stress on the importance of the egg-polarity maybe mentioned Auerbach ('74), Hatschek C77), Whitman C78), and Van Beneden ('83).


PROMORPHOLOGICAL RELATIONS OF CLEAVAGE 379

of the upper hemisphere represent the " animal layer," outer germlayer or ectoblast from which arise the epidermis, the nervous system, and the sense-organs. This fact, afterward confirmed in a very large number of animals, led to the designation of the two poles as animal and vegetative 1 formative and nutritive, or protoplasmic and deiitoplasmic, the latter terms referring to the fact that the nutritive deutoplasm is mainly stored in the lower hemisphere, and that development is therefore more active in the upper. The polarity of the ovum is accentuated by other correlated phenomena. In every case where an egg-axis can be determined by the accumulation of deutoplasm in the lower hemisphere the egg-nucleus sooner or later lies eccentrically in the upper hemisphere, and the polar bodies are formed at the upper pole. Even in cases where the deutoplasm is equally distributed or is wanting — if there really be such cases — an egg-axis is still determined by the eccentricity of the nucleus and the corresponding point at which the polar bodies are formed.

In vastly the greater number of cases the polarity of the ovum has a definite promorphological significance ; for the egg-axis shows a definite and constant relation to the axes of the adult body. It is a very general rule that the upper or ectodermic pole, as marked by the position of the polar bodies, lies in the median plane at a point which is afterward found to lie at or near the anterior end. Throughout the annelids and mollusks, for example, the upper pole is the point at which the cerebral ganglia are afterward formed ; and these organs lie in the adult on the dorsal side near the anterior extremity. This relation holds true for many of the Bilateralia, though the primitive relation is often disguised by asymmetrical growth in the later stages, such as occur in echinoderms. There is, however, some reason to believe that it is not a universal rule. The recent observations of Castle C96), which are in accordance with the earlier work of Seeliger, show that in the tunicate Ciona the usual relation is reversed, the polar bodies being formed at the vegetative {i.e. deutoplasmic or entodermic) pole, which afterward becomes the dorsal side of the larva. My own observations O95) on the echinoderm-egg indicate that here the primitive egg-axis has an entirely inconstant and casual relation to the gastrula-axis. It may, however, still be possible to show that these exceptions are only apparent, and the principle involved is too important to be accepted without further proof.

(6) Axial Relations of the Primary Cleavage-planes. — Since the egg-axis is definitely related to the embryonic axes, and since the first two cleavage-planes pass through it, we may naturally look for a definite relation between these planes and the embryonic axes ; and if such a relation exists, then the first two or four blastomeres must likewise have a definite prospective value in the development. Such


380 CELL-DIVISIQX AXD DEVELOPMENT

relations have, in fact, been accurately determined in a large number of cases. The first to call attention to such a relation seems to have been Newport ('541, who discovered the remarkable fact that the first cleavage-plane in the frog s egg coincides with Ike median plane of the adult body; that, in other words, one of the first two blastomeres gives rise to the left side of the body, the other to the right. This discover)', though long overlooked and, indeed, forgotten, was coofirmed more than thirty years later by Pfliigcr and Rou.x ('S/L It



tagc of the tunicate egg. .ed from the ventral side. B. Siiteen-cell stage |Va: 1 thiotgh Ihe gastrula stage (Castle) ; a. antetiot irmaiion according to Castle.]


was placed beyond all question by a remarkable experiment by Roux ('88), who succeeded in killing one of the blastomeres by puncture with a heated needle, whereupon the uninjured cell gave rise to a half-body as if the embryo had been bisected down the middle line (Fig. 182).

A similar result has been reached in a number of other animals by following out the cell-lineage; e.g. by Van Beneden and Julin ('84)


PROMORPHOLOGLCAL RELATIONS OF CLEAVAGE 38I

in the egg of the tunicate Clavelina (Fig. 177), and by Watase ('91) in the eggs of cephalopods (Fig. 178). In both these cases all the early stages of cleavage show a beautiful bilateral symmetry, and not only can the right and left halves of the segmenting egg be distinguished with the greatest clearness, but also the anterior and posterior regions, and the dorsal and ventral aspects. These discoveries seemed, at first, to justify the hope that a fundamental law of development had been discovered, and Van" Beneden was thus led, as early as 18S3, to express the view that the development of all bilateral animals would probably be found to agree with the frog and ascidian in respect to the relations of the first cleavage.

This cleavage was soon proved to have been premature. In one series of forms, not the first but the second cleavage-plane was found



Fig. 178. — Bilateral cleavage of the squill's e A. Eight-cell stage. B. The fifth cleavage in progress. The first cleavage {a-f) coincide) with the future median plane ; the second (l-r) is transverse.

to coincide with the future long axis {Nereis, and some other annelids ; Crepidula, Umbrella, and other gasteropods). In another series of forms neither of the first cleavages passes through the median plane, but both form an angle of about 45 to it {Clcpsine and other leeches ; Rhynclulmis and other annelids ; Planorbis, Nassa, Unio, and other mollusks; Dtscoecelis and other platodes). In a few cases the first cleavage departs entirely from the rule, and is equatorial, as in Ascaris and some other nematodes. The whole subject was finally thrown into apparent confusion, first by the discovery of Clapp ('91 ), Jordan, and Eycleshymer ('94) that in some cases there seems to be no constant relation whatever between the early cleavage-planes and the adult axes, even in the same species (teleosts, urodeles) ; and even in


382


CELL-DIVISION AND DEVELOPMENT


the frog Hertwig showed that the relation described by Newport and Roux is not invariable. Driesch finally demonstrated that the direction of the early cleavage-planes might be artificially modified by pressure without perceptibly affecting the end-result (cf. p. 375).

These facts prove that the promorphology of the early cleavageforms can have no fundamental significance. Nevertheless, they are of the highest interest and importance ; for the fact that the formative forces by which development is determined may or may not coincide with those controlling the cleavage, gives us some hope of



v v

Fig- 1 79- ~ Outline of unsegmented squid's egg, to show bilaterality. [Watas#.] A. From right side. B. From posterior aspect. a-p. antero-posterior axis ; d-v. dorso-ventral axis ; /. left side ; r. right side.


disentangling the complicated factors of development through a comparative study of the different forms.

(c) Other P romorphological Characters of the Ovum. — Besides the polarity of the ovum, which is the most constant and clearly marked of its promorphological features, we are often able to discover other characters that more or less clearly foreshadow the later development. One of the most interesting and clearly marked of these is the bilateral symmetry of the ovum in bilateral animals, which is sometimes so clearly marked that the exact position of the embryo may be predicted in the unfertilized egg, sometimes even before it is laid. This is the case, for example, in the cephalopod egg, as shown by Watase (Fig. 179). Here the form of the new-laid egg, before cleavage begins, distinctly foreshadows that of the embryonic bodv, and forms as it were a mould in which the whole development is cast. Its general shape is that of a hen's egg slightly flattened on one side,


PRQMORPHQLQGICAL RELATIONS Of CLEAVAGE 383

the narrow end, according to Watase, representing the dorsal aspect, the broad end the ventral aspect, the flattened side the posterior region, and the more convex side the anterior region. All the early cleavage-furrows are bilaterally arranged with respect to the plane of



Fig. 180. — Eggs of the it

A. Earl]' stage before formation of the ei

plane of symmetry. C. The embryo in its fir

a. anterior end ; p. posterior ; /. left side,

refer to xhejSital position of the embryo, whi

first develops) ; m.micropyle. near p is the


31 Cerira, [MF.TSCHNtKOFF.]


re side. 13. The

il, d. dorsal aspect. (These


viewed in the


symmetry in the undivided egg; and the same is true of the later development of all the bilateral parts.

Scarcely less striking is the case of the insect egg, as has been pointed out especially by Hallez, Blochmann, and Wheeler (Figs. 62, 180). In a large number of cases the egg is elongated and


384 CELL-DJ VISION AND DEVELOPMENT

bilaterally symmetrical, and, according to Blochmann and Wheeler, may even show a bilateral distribution of the yolk corresponding with the bilaterality of the ovum. Hallez asserts as the results of a study of the cockroach (Periplaneta), the water-beetle {Hydrophilus\ and the locust (Locusta) that "the egg-cell possesses the same orientation as the maternal organism that produces it ; it has a cephalic pole and a caudal pole, a light side and a left, a dorsal aspect and a ventral ; and these different aspects of the egg-cell coincide with the corresponding aspects of the embryo." 1 Wheeler ('93), after examining some thirty different species of insects, reached the same result, and concluded that even when the egg approaches the spherical form the symmetry still exists, though obscured. Moreover, according to Hallez ('86) and later writers, the egg always lies in the same position in the oviduct, its cephalic end being turned forwards toward the upper end of the oviduct, and hence toward the head-end of the mother. 2

2. Meaning of the Promorphology of the Ovum

The interpretation of the promorphology of the ovum cannot be adequately treated apart from the general discussion of development given in the following chapter; nevertheless it may briefly be considered at this point. Two widely different interpretations of the facts have been given. On the one hand, it has been suggested by Flemming and Van Beneden, 8 and urged especially by Whitman, 4 that the cytoplasm of the ovum possesses a definite primordial organization which exists from the beginning of its existence even though invisible, and is revealed to observation thiough polar differentiation, bilateral symmetry, and other obvious characters in the unsegmented egg. On the other hand, it has been maintained by Pfluger, Mark, Oscar Hertwig, Driesch, Watas£, and the writer that all the promorphological features of the ovum are of secondary origin; that the egg-cytoplasm is at the beginning isotropous — i.e. indifferent or homaxial — and gradually acquires its promorphological features during its preembryonic history. Thus the egg of a bilateral animal is at the beginning not actually, but only potentially, bilateral. Bilaterality once established, however, it forms as it were the mould in which the cleavage and other operations of development are cast

I believe that the evidence at our command weighs heavily on the side of the second view, and that the first hypothesis fails to

1 See Wheeler, '93, p. 67.

2 The micropyle usually lies at or near the anterior end, but may be at the posterior. It is a very important fact that the position of the polar bodies varies, being sometimes at the anterior end, sometimes on the side, either dorsal or lateral (Heider, Blochmann).

8 See p. 298. 4 Cf. pp. 299, 300.


PROMORPHOLOGICAL RELATIONS OF CLEAVAGE 385

take sufficient account of the fact that development does not necessarily begin with fertilization or cleavage, but may begin at a far earlier period during ovarian life. As far as the visible promorphological features of the ovum are concerned, this conclusion is beyond question. The only question that has any meaning is whether these visible characters are merely the expression of a more subtle pre


Plg. 181. — Variations 111 the axial re] as they lie in the oviduct. [Hacker.]

A. Group of eggs showing variations in relative position of the polar spindles and (he spermnucleus (the latter black) ; in a the sperm-nucleus is opposite lo the polar spindle, in b, near il or at the side. B. Group showing variations in the axis of first cleavage with reference to the polar bodies (the latter black ) ; a, b, and c show three different positions.


existing invisible organization of the same kind. I do not believe that this question can be answered in the affirmative save by the trite and, from this point of view, barren statement that every effect must have its preexisting cause. That the egg possesses no fixed and predetermined cytoplasmic localization with reference to the adult parts, has, I think, been demonstrated through the remarkable


386 CELL-DIVISION AND DEVELOPMENT

m

experiments of Driesch, Roux, and Boveri, which show that a fragment of the egg may give rise to a complete larva (p. 353). There is strong evidence, moreover, that the egg-axis is not primordial but is established at a particular period ; and even after its establishment it may be entirely altered by new conditions. This is proved, for example, by the case of the frog's egg, in which, as Pfluger ('84), Born ('85), and Schultze ('94) have shown, the cytoplasmic materials may be entirely rearranged under the influence of gravity, and a new axis established. In sea-urchins, my own observations C95) render it probable that the egg-axis is not finally established until after fertilization. These and other facts, to be more fully considered in the following chapter, give strong ground for the conclusion that the promorphological features of the egg are as truly a result of development as the characters coming into view at later stages. They are gradually established during the preembryonic stages, and the egg, when ready for fertilization, has already accomplished part of its task by laying the basis for what is to come.

Mark, who was one of the first to examine this subject carefully, concluded that the ovum is at first an indifferent or homaxial cell (i.e. isotropic), which afterward acquires polarity and other promorphological features. 1 The same* view was very precisely formulated by Watas6 in 1891, in the following statement, which I believe to express accurately the truth : *' It appears to me admissible to say at present that the ovum, which may start out without any definite axis at first, may acquire it later, and at the moment ready for its cleavage the distribution of its protoplasmic substances may be such as to exhibit a perfect symmetry, and the furrows of cleavage may have a certain definite relation to the inherent arrangement of the protoplasmic substances which constitute the ovum. Hence, in a certain case, the plane of the first cleavage-furrow may coincide with the plane of the median axis of the embryo, and the sundering of the protoplasmic material may take place into right and left, according to the preexisting organization of the c^g at the time of cleavage ; and in another case the first cleavage may roughly correspond to the differentiation of the ectoderm and the entoderm, also according to the preorganized constitution of the protoplasmic materials of the ovum.

" It does not appear strange, therefore, that we may detect a certain structural differentiation in the unsegmented ovum, with all the axes foreshadowed in it, and the axial symmetry of the embryonic organism identical with that of the adult." 2

This passage contains, I believe, the gist of the whole matter, as far as the promorphological relations of the ovum and of cleavage lf 8i, p. 512. a '9i,p. 280.


PROMORPHOLOGICAL RELATIONS OF CLEAVAGE 387

forms are concerned, though Watas6 does not enter into the question as to how the arrangement of protoplasmic materials is effected. In considering this question, we must hold fast to the fundamental fact that the egg is a cell, like other cells, and that from an a priori point of view there is every reason to believe that the cytoplasmic differentiations that it undergoes must arise in essentially the same way as in other cells. We know that such differentiations, whether in form or in internal structure, show a definite relation to the environment of the cell — to its fellows, to the source of food, and the like. We know further, as Korschelt especially has pointed out, that the eggaxis, as expressed by the eccentricity of the germinal vesicle, often shows a definite relation to the ovarian tissues, the germinal vesicle lying near the point of attachment or of food-supply. Mark made the pregnant suggestion, in 1881, that the primary polarity of the egg might be determined by " the topographical relation of the egg (when still in an indifferent state) to the remaining cells of the maternal tissue from which it is differentiated" and added that this relation might operate through the nutrition of the ovum. " It would certainly be interesting to know if that phase of polar differentiation which is manifest in the position of the nutritive substance and of the germinal vesicle bears a constant relation to the free surface of the epithelium from which the egg takes its origin. If, in cases where the egg is directly developed from epithelial cells, this relationship were demonstrable, it would be fair to infer the existence of corresponding, though obscured, relations in those cases where (as, for example, in mammals) the origin of the ovum is less directly traceable to an epithelial surface." 1 The polarity of the egg would therefore be comparable to the polarity of epithelial or gland-cells, where, as pointed out at page 57, the nucleus usually lies toward the base of the cell, near the source of food, while the centrosomes, and often also characteristic cytoplasmic products, such as zymogen granules and other secretions, appear in the outer portion. 2 The exact conditions under which the ovarian egg develops are still too little known to allow of a positive conclusion regarding Mark's suggestion. Moreover, the force of Korschelt's observation is weakened by the fact that in many eggs of the extreme telolecithal type, where the polarity is very marked, the germinal vesicle occupies a central or sub-central position during the period of yolk-formation and only moves toward the periphery near the time of maturation.

Indeed, in mollusks, annelids, and many other cases, the germinal vesicle remains in a central position, surrounded by yolk on all sides, until the spermatozoon enters. Only then does the egg-nucleus move

^Si.p. 515.

2 Hatschek has suggested the same comparison (ZoMogit, p. 112).


388 CELL-DIVISION AND DEVELOPMENT

to the periphery, the deutoplasm become massed at one pole, and the polarity of the egg come into view {Nereis, Figs. 60 and 97). 1 In such cases the axis of the egg may perhaps be predetermined by the position of the centrosome, and we have still to seek the causes by which the position is established in the ovarian' history of the egg. These considerations show that this problem is a complex one, involving, as it does, the whole question of cell-polarity ; and I know of no more promising field of investigation than the ovarian history of the ovum with reference to this question. That Mark's view is correct in principle is indicated by a great array of general evidence considered in the following chapter, where its bearing on the general theory of development is more fully dealt with.

C. Cell-division and Growth

The general relations between cell-division and growth, which have already been briefly considered at page 58 and in the course of this chapter, may now be more critically examined, together with some account of the causes that incite or inhibit division. It has been shown above that every precise inquiry into the rate form, or direction of cell-division, inevitably merges into the larger problem of the general determination of growth. We may conveniently approach this subject by considering first the energy of division and the limitation of growth.

All animals and plants have a limit of growth, which is, however, much more definite in some forms than in others, and differs in different tissues. During the individual development the energy of cell-division is most intense in the early stages (cleavage) and diminishes more and more as the limit of growth is approached. When the limit is attained a more or less definite equilibrium is established, some of the cells ceasing to divide and perhaps losing this power altogether (nerve-cells), others dividing only under special conditions (connective tissue-cells, gland-cells, muscle-cells), while others continue to divide throughout life, and thus replace the worn-out cells of the same tissue (Malpighian layer of the epidermis, etc.). The limit of size at which this state of equilibrium is attained is an hereditary character, which in many cases shows an obvious relation to the environment, and has therefore probably been determined and is maintained by natural selection. From the cytological point of view the limit of body-size appears to be correlated with the total number of cells formed rather than with their individual size. This relation has been carefully studied by Conklin C96) in the case of the gastero 1 The immature egg of Nereis show's, however, a distinct polarity in the arrangement of the fat-drops, which form a ring in the equatorial regions.


CELL-DIVISION AND GROWTH 389

pod Crepidula, an animal which varies greatly in size in the mature condition, the dwarfs having in some cases not more than ^ the volume of the giants. The eggs are, however, of the same size in all, and their number is proportional to the size of the adult. The same is true of the tissue-cells. Measurements of cells from the epidermis, the kidney, the liver, the alimentary epithelium, and other tissues show that they are on the whole as large in the dwarfs as in the giants. The body-size therefore depends on the total number of cells rather than on their size individually considered, and the same appears to be the case in plants. 1

A result which, broadly speaking, agrees with the foregoing, is given through the interesting experimental studies of Morgan ('95, 1, '96), supplemented by those of Driesch ('98), in which the number of cells in normal larvae of echinoderms, ascidians, and Amphioxus is compared with those in dwarf larvae of the same species developed from egg-fragments (Morgan) and isolated blastomeres (Driesch). Unless otherwise specified, the following data are cited from Driesch.

The normal blastula of Spharechinus possesses about 500 cells (Morgan), of which from 75 to 90 invaginate to form the archenteron (Driesch). In half-gastrulas the number varies from 35^045, occasionally reaching 50. In the same species, the normal number of mesenchyme-cells is 54 to 60, in the half-larvae 25 to 30. In Echinus the corresponding numbers are 30± and 13 to 15. In the ascidian larvae — a particularly favourable object — there are 29 to 35 (exceptionally as high as 40) chorda-cells ; in the hapf-larvae, 1 3 to 17. While these comparisons are not mathematically prfecise, owing to the difficulty of selecting exactly equivalent stages, they nevertheless show that, on the whole, the size of the organ, as of the entire organism, is directly proportional to the number and not to the size of the cells, just as in the mature individuals of Crepidula. The available data are, however, too scanty to justify any very positive conclusions, and it is probable that further experiment will disclose factors at present unknown. It would be highly interesting to determine whether such dwarf embryos could in the end restore the normal number of cells, and, hence, the normal size of the body. In all the cases thus far determined the dwarf gastrulas give rise to larvae (Plutci, etc.) correspondingly dwarfed ; but their later history has not yet been sufficiently followed out.

The gradual diminution of the energy of division during development by no means proceeds at a uniform pace in all of the cells, and, during the cleavage, the individual blastomeres are often found to exhibit entirely different rhythms of division, periods of active division being succeeded by long pauses, and sometimes by an entire cessa 1 See Amelung ('93) and Strasburger ('93).


390 CELL-DIVISION AND DEVELOPMENT

tion of division even at a very early period. In the echinoderms, for example, it is well established that division suddenly pauses, or changes its rhythm, just before the gastrulation (in Synapta at the 512-cell stage, according to Selenka), and the same is said to be the case in Amphioxus (Hatschek, Lwoff ). In Nereis, one of the blastomeres on each side of the body in the forty-two-cell stage suddenly ceases to divide, migrates into the interior of the body, and is converted into a unicellular glandular organ. 1 In the same animal, the four lower cells (macromeres) of the eight-cell stage divide in nearly regular succession up to the thirty-eight-cell stage* when a long pause takes place, and when the divisions are resumed they are of a character totally different from those of the earlier period. The cells of the ciliated belt or prototroch in this and other annelids likewise cease to divide at a certain period, their number remaining fixed thereafter. 2 Again, the number of cells produced for the foundation of particular structures is often definitely fixed, even when their number is afterward increased by division. In annelids and gasteropods, for example, the entire ectoblast arises from twelve micromeres segmented off in three successive quartets of micromeres from the blastomeres of the fourcell stage. Perhaps the most interesting numerical relations of this kind are those recently discovered in the division of teloblasts, where the number of divisions is directly correlated with the number of segments or somites. It is well known that this is the case in certain plants (Characece\ where the. alternating nodes and internodes of the stem are derived from corirMxmding single cells successively segmented off from the apical dSif Vejdovsky's observations on the annelid Dcndrobana give strong ground to believe that the number of metamerically repeated parts of this animal, and probably of other annelids, corresponds in like manner with that of the number of cells segmented off from the teloblasts. The most remarkable and accurately determined case of this kind is that of the isopod Crustacea, where the number of somites is limited and perfectly constant. In the embryos of these animals there are two groups of teloblasts near the hinder end of the embryo, viz. an inner group of mesoblasts, from which arise the mesoblast-bands, and an outer group of ectoblasts, from which arise the neural plates and the ventral ectoblast. McMurrich ('95) has recently demonstrated that the mesoblasts always divide exactly sixteen times, the ectoblasts thirty-two (or thirty-three) times, before relinquishing their teleoblastic mode of division and breaking up into smaller cells. Now the sixteen groups of cells thus formed give rise to the sixteen respective somites of the post-naupliar region of the embryo {i.e. from the second maxilla backward). In other

1 This organ, doubtfully identified by me as the head-kidney, is probably a mucus-gland (Mead). 2 Cf. Fig. 171.


CELLr-DI VISION AND GROWTH 39 1

words, each single division of the mesoblasts and each double division of the ectoblasts splits off the material for a single somite ! The number of these divisions, and hence of the corresponding somites, is a fixed inheritance of the species.

The causes that determine the rhythm of division, and thus finally establish the adult equilibrium, are but vaguely comprehended. The ultimate causes must of course lie in the inherited constitution of the organism, and are referable in the last analysis to the structure -of the germ-cells. Every division must, however, be the response of the cell to a particular set of conditions or stimuli ; and it is through the investigation of these stimuli that we may hope to penetrate farther into the nature of development. The immediate, specific causes of cell-division are still imperfectly known. In the adult, cells may be stimulated to divide by the utmost variety of agencies — by chemical stimulus, as in the formation of galls, or in hyperplasia induced by the injection of foreign substances into the blood ; by mechanical pressure, as in the formation of calluses ; by injury, as in the healing of wounds and in the regeneration of lost parts ; and by a multitude of more complex physiological and pathological conditions, — by any agency, in short, that disturbs the normal equilibrium of the body. In all these cases, however, it is difficult to determine the immediate stimulus to division ; for a long chain of causes and effects may intervene between the primary disturbance and the ultimate reaction of the dividing cells. Thus there is reason to believe that the formation of a callus is not directly caused by pressure or friction, but through the determination of an increased blood-supply to the part affected and a heightened nutrition of the cells. Cell-division is here probably incited by local chemical changes ; and the opinion is gaining ground that the immediate causes of division, whatever their antecedents, are to be sought in this direction. That such is the case is indicated by nothing more clearly than the recent experiments on the egg by R. Hertwig, Mead, Morgan, and Loeb already referred to in part at pages 1 1 1 and 215. The egg-cell is, in most cases, stimulated to divide by the entrance of the spermatozoon, but in parthenogenesis exactly the same result is produced by an apparently quite different cause. The experiments in question give, however, ground for the conclusion that the common element in the two cases is a chemical stimulus. In the eggs of Chatopterus under normal conditions the first polar mitosis pauses at the anaphase until the entrance of the spermatozoon, when the mitotic activity is resumed and both polar bodies are formed. Mead C98) shows, however, that the same effect may be produced without fertilization by placing the eggs for a few minutes in a weak solution of potassium chloride. In like manner R. Hertwig ('96) and Morgan ('99) show that unfertilized


392 CELL-DIVISION AND DEVELOPMENT

echinoderm-eggs may be stimulated to division by treatment with weak solution of strychnine, sodium-chloride, and other reagents, the result being here more striking than in the case of Chcetopterus, since the entire mitotic system is formed anew under the chemical stimulus. The climax of these experiments is reached in Loeb's artificial production of parthenogenesis in sea-urchin eggs by treatment with dilute magnesium chloride. Beside these interesting results may be placed the remarkable facts of gall-formation in plants, which seem to leave no doubt that extremely complex and characteristic abnormal growths may result from specific chemical stimuli, and many pathologists have held that tumours and other pathological growths in the animal body may be incited through disturbances of circulation or other causes resulting in abnormal local chemical conditions. 1

But while we have gained some light on the immediate causes of division, we have still to inquire how those causes are set in operation and are coordinated toward a typical end ; and we are thus brought again to the general problem of growth. A very interesting suggestion is the resistance-theory of Thiersch and Boll, according to which each tissue continues to grow up to the limit afforded by the resistance of neighbouring tissues or organs. The removal or lessening of this resistance through injury or disease causes a resumption of growth and division, leading either to the regeneration of the lost parts or to the formation of abnormal growths. Thus the removal of a salamander's limb would seem to remove a barrier to the proliferation and growth of the remaining cells. These processes are therefore resumed, and continue until the normal barrier is reestablished by the regeneration. To speak of such a "barrier" or "resistance" is, however, to use a highly figurative phrase which is not to be construed in a rude mechanical sense. There is no doubt that hypertrophy, atrophy, or displacement of particular parts often leads to compensatory changes in the neighbouring parts ; but it is equally certain that such changes are not a direct mechanical effect of the disturbance, but a highly complex physiological response to it. How complex the problem is, is shown by the fact that even closely related animals may differ widely in this respect. Thus Fraisse has shown that the salamander may completely regenerate an amputated limb, while the frog only heals the wound without further regeneration. 2 Again, in the case of coelenterates, Loeb and Bickford have shown that the tubularian hydroids are able to regenerate the tentacles at both ends of a segment of the stem, while the polyp Cerianthus can regenerate them only at the distal end of a section (Fig. 194).

1 Cf. p. 97. For a good discussion of this subject, see E. Ziegler, '89.

2 In salamanders regeneration only takes place when the bone is cut across, and does not occur if the limb be exarticulated and removed at the joint.


In the latter case, therefore, the body possesses an inherent polarity which cannot be overturned by external conditions. A very curious case is that of the earthworm, which has long been known to possess a high regenerative capacity. If the posterior region of the worm be cut off, a new tail is usually regenerated. If the same operation be performed far forward in the anterior region, a new head is often formed at the front end of the posterior piece. If, however, the section be in the middle region the posterior piece sometimes regenerates a head, but more usually a tail, as was long since shown by Spallanzani and recently by Morgan ('99). Why such a blunder should be committed remains for the present quite unexplained.

It remains to inquire more critically into the nature of the correlation between growth and cell-division. In the growing tissues the direction of the division-planes in the individual cells evidently stands in a definite relation with the axes of growth in the body, as is especially clear in the case of rapidly elongating structures (apical buds, teloblasts, and the like), where the division-planes are predominantly transverse to the axis of elongation. Which of these is the primary factor, the direction of general growth or the direction of the divisionplanes ? This question is a difficult one to answer, for the two phenomena are often too closely related to be disentangled. As far as the plants are concerned, however, it has been conclusively shown by Hofmeister, De Bary, and Sachs that the growth of the mass is the primary factor ; for the characteristic mode of growth is often shown by the growing mass before it splits up into cells, and the form of cell-division adapts itself to that of the mass : " Die Pflanze bildet Zellen, nicht die Zelle bildet Pflanzen " (De Bary).

Much of the recent work in normal and experimental embryology, as well as that on regeneration, indicates that the same is true in principle of animal growth. Among recent writers who have urged this view should be mentioned Rauber, Hertwig, Adam Sedgwick, and especially Whitman, whose fine essay on the Inadequacy of the Celltheory of Development C93) marks a distinct advance in our point of view. Still more recently this view has been almost demonstrated through some remarkable experiments on regeneration, which show that definitely formed material, in some cases even the adult tissues, may be directly moulded into new structures. Driesch has shown (95» 2 » 99) that if gastrulas of Sphcerechinus be bisected through the equator so that each half contains both ectoderm and entoderm, the wounds heal, each half forming a typical gastrula, in which the enteron differentiates itself into the three typical regions (fore, middle, and hind gut) correctly proportioned, though the whole structure is but half the normal size. Here, therefore, the formative process is in the main independent of cell-division or increase in size. Miss Bickf ord


('94) found that in the regeneration of decapitated hydranths of tubalarians the.new hydranth is primarily formed, not by new cell-formation and growth from the cut end, but by direct- transformation of the distal portion of the stem. 1 Morgan's remarkable observations on Planaria, finally, show that here also, when the animal is cut into pieces, complete animals are produced from these pieces, but only in small degree through the formation of new tissue, and mainly by direct remoulding of the old material into a new body having the correct proportions of the species. As Driesch has well said, it is as if a plan or mould of the new little worm were first prepared and then the old material were poured into it. 2

Facts of this kind, of which a considerable store has been accumulated, give strong ground for the view that cell-formation is subordinate to growth, or rather to the general formative process of which growth is an expression ; and they furnish a powerful argument against Schwann's conception of the organism as a cell-composite (p. 58). That conception is, however, not to be rejected in Mo, but contains a large element of truth ; for there are many cases in which cells possess so high a degree of independence that profound modifications may occur in special regions through injury or disease, without affecting the general equilibrium of the body. The most striking proof of this lies in the fact that grafts or transplanted structures may perfectly retain their specific character, though transferred to a different region of the body, or even to another species. Nevertheless the facts of regeneration prove that even in the adult the formative processes in special parts are in many cases definitely correlated with the organization of the entire mass ; and there is reason to conclude that such a correlation is a survival, in the adult, of a condition characteristic of the embryonic stages, and that the independence of special parts in the adult is a secondary result of development. The study of celldivision thus brings us finally to a general consideration of development which forms the subject of the following chapter.

Literature

Bert hold, G. — Studien uber Protoplasma-mechanik. IMpzig, 1886.

Boll, Fr. — Das Frincip des Wachsthums. Berlin, 1876.

Bourne, G. C. — A Criticism of the Cell-theory ; being an answer to Mr. Sedgwick's

article on the Inadequacy of the Cellular Theory of Development : Quart. Journ.

Mic.Sci., XXXVIII. 1. 1895.

1 Driesch suggests for such a process the term reparation in contradistinction to true regeneration.

- '99, p. 55. It is mainly on these considerations that Driesch ('99) has built his recent theory of vitalism (ef. p. 417), the nature of the formative power being regarded as a problem sui generis, and one which the " machine-theory of life " is powerless to solve. Cf. also the views of Whitman, p. 416.

Castle, W. E.— The early Embryology of Ciona. Bull. Mus. Comp. Zoo/., XXVII.

1896. Conklin, E. G. — The Embryology of Crepidula : Journ. Morph., XIII. 1897. Driesch, H. — (See Literature, IX.) Errera, L. — Zellformen und Seifenblasen : Tagebl. der 60 Versammlung deutscher

Naturforscher und Aerste zu Wiesbaden. 1887. Hertwig, 0. — Das Problem der Befruchtung und der Isotropic des Eies, eine Theo rie der Vererbung. Jena* 1884. Hofmeister. — Die Lehre von der Pflanzenzelle. Leipzig, 1867. Jennings, H. S. — The Early Development of Asplanchna : Bull. Mus. Comp. Zodl.*

XXX. 1. Cambridge, 1896. Kofoid, C. A. — On the Early Development of Limax : Bull. Mus. Comp. Zool.,

XXVII. 1895. Lillie, F. R. — The Embryology of the Unionidae : Journ. Morph.* X. 1895. Id. — Adaptation in Cleavage : H'ood^s Holl Biol. lectures. 1899. McMurrich, J. P. — Embryology of the Isopod Crustacea: Journ. Morph., XI. 1.

1895. Mark, E. L. — Limax. (See list IV.) Morgan, T. H. — (See Literature, IX.) fiauber, A. — Neue Grundlegungen zur Kenntniss derZelle: Morph. Jahrb., VIII.

1883. Rhumbler, L. — Allgemeine Zellmechanik : Merkel u. Bonnet, Ergeb., VIII. 1898. Sachs, J. — Pflanzenphysiologie. (See list VII.) Sedgwick, H. — On the Inadequacy of the Cellular Theory of Development, etc. :

Quart. Journ . Mic. Sci. , XXX V 1 1 . 1 . 1 894. Strasburger, E. — Uber die Wirkungssphare der Kerne und die Zellgrbsse : Histo logische Beitrdge, V. 1893. Zur Strassen. 0. — Embryonalentwickelung der Ascaris : Arch. Entom.* III. 1896. Watasl, S. — Studies on Cephalopods ; I., Cleavage of the Ovum : Journ. Morph.,

IV. 3. 1891. Whitman, C. 0. — The Inadequacy of the Cell-theory of Development : Wood^s Holl

Biol. Lectures. 1893. Wilson, Edm. B. — The Cell-lineage of Nereis: Journ. Morph., VI. 3. 1892. Id. — Amphioxus and the Mosaic Theory of Development : Journ. Morph.* VIII. 3.

. 1893. Id. — Considerations on Cell-lineage and Ancestral Reminiscence: Ann. N. Y.

Acad. , XI. 1898: also Wood \r Holl Biol. Lectures* 1899.



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   Cell development and inheritance (1900): Introduction | List of Figures | Chapter I General Sketch of the Cell | Chapter II Cell-division | Chapter III The Germ-cells | Chapter IV Fertilization of the Ovum | Chapter V Reduction of the Chromosomes, Oogenesis and Spermatogenesis | Chapter VI Some Problems of Cell-organization | Chapter VII Some Aspects of Cell-chemistry and Cell-physiology | Chapter VIII Cell-division and Development | Chapter IX Theories of Inheritance and Development | Glossary

Wilson EB. The Cell in Development and Inheritance. Second edition (1900) New York, 1900.


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