Inembryology,cleavage is the division ofcells in the earlydevelopment of the embryo, followingfertilization.[1] Thezygotes of many species undergo rapidcell cycles with no significant overall growth, producing a cluster of cells the same size as the original zygote. The different cells derived from cleavage are calledblastomeres and form a compact mass called themorula. Cleavage ends with the formation of theblastula, or of theblastocyst in mammals.
Depending mostly on the concentration ofyolk in the egg, the cleavage can beholoblastic (total or complete cleavage) ormeroblastic (partial or incomplete cleavage). The pole of the egg with the highest concentration of yolk is referred to as thevegetal pole while the opposite is referred to as theanimal pole.
Cleavage differs from other forms ofcell division in that it increases the number of cells andnuclear mass without increasing thecytoplasmic mass. This means that with each successive subdivision, there is roughly half the cytoplasm in each daughter cell than before that division, and thus the ratio of nuclear to cytoplasmic material increases.[2]
The rapid cell cycles are facilitated by maintaining high levels of proteins that control cell cycle progression such as thecyclins and their associatedcyclin-dependent kinases (CDKs). The complexcyclin B/CDK1 also known as MPF (maturation promoting factor) promotes entry into mitosis.
The processes ofkaryokinesis (mitosis) andcytokinesis work together to result in cleavage. The mitotic apparatus is made up of acentral spindle and polarasters made up of polymers oftubulin protein calledmicrotubules. The asters are nucleated bycentrosomes and the centrosomes are organized by centrioles brought into the egg by the sperm asbasal bodies. Cytokinesis is mediated by thecontractile ring made up of polymers ofactin protein calledmicrofilaments. Karyokinesis and cytokinesis are independent but spatially and temporally coordinated processes. While mitosis can occur in the absence of cytokinesis, cytokinesis requires the mitotic apparatus.
The end of cleavage coincides with the beginning of zygotic transcription. This point in non-mammals is referred to as themidblastula transition and appears to be controlled by thenuclear-cytoplasmic ratio (about 1:6).
Determinate cleavage (also called mosaic cleavage) is in mostprotostomes. It results in the developmental fate of thecells being set early in theembryodevelopment. Each blastomere produced by early embryonic cleavage does not have the capacity to develop into a completeembryo.
A cell can only be indeterminate (also called regulative) if it has a complete set of undisturbed animal/vegetal cytoarchitectural features. It is characteristic ofdeuterostomes—when the original cell in a deuterostome embryo divides, the two resulting cells can be separated, and each one can individually develop into a whole organism.
In holoblastic cleavage, the zygote and blastomeres are completely divided during the cleavage, so the number of blastomeres doubles with each cleavage. In the absence of a large concentration of yolk, four major cleavage types can be observed inisolecithal cells (cells with a small, even distribution of yolk) or in mesolecithal cells or microlecithal cells (moderate concentration of yolk in a gradient)—bilateral holoblastic,radial holoblastic,rotational holoblastic, andspiral holoblastic, cleavage.[3] These holoblastic cleavage planes pass all the way through isolecithal zygotes during the process of cytokinesis. Coeloblastula is the next stage of development for eggs that undergo these radial cleavages. In holoblastic eggs, the first cleavage always occurs along the vegetal-animal axis of the egg, the second cleavage is perpendicular to the first. From here, the spatial arrangement of blastomeres can follow various patterns, due to different planes of cleavage, in various organisms.
The first cleavage results in bisection of the zygote into left and right halves. The following cleavage planes are centered on this axis and result in the two halves being mirror images of one another. In bilateral holoblastic cleavage, the divisions of the blastomeres are complete and separate; compared with bilateral meroblastic cleavage, in which the blastomeres stay partially connected.
Radial cleavage is characteristic of thedeuterostomes, which include somevertebrates andechinoderms, in which the spindle axes are parallel or at right angles to the polar axis of theoocyte.
Rotational cleavage involves a normal first division along the meridional axis, giving rise to two daughter cells. The way in which this cleavage differs is that one of the daughter cells divides meridionally, whilst the other divides equatorially.
ThenematodeC. elegans, a popular developmentalmodel organism, undergoes holoblastic rotational cell cleavage.[4]
Spiral cleavage is conserved between many members of thelophotrochozoan taxa, referred to asSpiralia.[5] Most spiralians undergo equal spiral cleavage, although some undergo unequal cleavage (see below).[6] This group includesannelids,molluscs, andsipuncula. Spiral cleavage can vary between species, but generally the first two cell divisions result in four macromeres, also calledblastomeres, (A, B, C, D) each representing one quadrant of the embryo. These first two cleavages are not oriented in planes that occur at right angles parallel to the animal-vegetal axis of thezygote.[5] At the 4-cell stage, the A and C macromeres meet at the animal pole, creating the animal cross-furrow, while the B and D macromeres meet at the vegetal pole, creating the vegetal cross-furrow.[7] With each successive cleavage cycle, the macromeres give rise to quartets of smallermicromeres at the animal pole.[8][9] The divisions that produce these quartets occur at an oblique angle, an angle that is not a multiple of 90 degrees, to the animal-vegetal axis.[9] Each quartet of micromeres is rotated relative to their parent macromere, and the chirality of this rotation differs between odd- and even-numbered quartets, meaning that there is alternating symmetry between the odd and even quartets.[5] In other words, the orientation of divisions that produces each quartet alternates between being clockwise and counterclockwise with respect to the animal pole.[9] The alternating cleavage pattern that occurs as the quartets are generated produces quartets of micromeres that reside in the cleavage furrows of the four macromeres.[7] When viewed from the animal pole, this arrangement of cells displays a spiral pattern.
Specification of the D macromere and is an important aspect of spiralian development. Although the primary axis, animal-vegetal, is determined duringoogenesis, the secondary axis, dorsal-ventral, is determined by the specification of the D quadrant.[9] The D macromere facilitates cell divisions that differ from those produced by the other three macromeres. Cells of the D quadrant give rise to dorsal and posterior structures of the spiralian.[9] Two known mechanisms exist to specify the D quadrant. These mechanisms include equal cleavage and unequal cleavage.
Inequal cleavage, the first two cell divisions produce four macromeres that are indistinguishable from one another. Each macromere has the potential of becoming the D macromere.[8] After the formation of the third quartet, one of the macromeres initiates maximum contact with the overlying micromeres in the animal pole of the embryo.[8][9] This contact is required to distinguish one macromere as the official D quadrant blastomere. In equally cleaving spiral embryos, the D quadrant is not specified until after the formation of the third quartet, when contact with the micromeres dictates one cell to become the future D blastomere. Once specified, the D blastomere signals to surrounding micromeres to lay out their cell fates.[9]
Inunequal cleavage, the first two cell divisions are unequal producing four cells in which one cell is bigger than the other three. This larger cell is specified as the D macromere.[8][9] Unlike equally cleaving spiralians, the D macromere is specified at the four-cell stage during unequal cleavage. Unequal cleavage can occur in two ways. One method involves asymmetric positioning of the cleavage spindle.[9] This occurs when theaster at one pole attaches to the cell membrane, causing it to be much smaller than the aster at the other pole.[8] This results in an unequalcytokinesis, in which both macromeres inherit part of the animal region of the egg, but only the bigger macromere inherits the vegetal region.[8] The second mechanism of unequal cleavage involves the production of an enucleate, membrane bound, cytoplasmic protrusion, called a polar lobe.[8] This polar lobe forms at the vegetal pole during cleavage, and then gets shunted to the D blastomere.[7][8] The polar lobe contains vegetal cytoplasm, which becomes inherited by the future D macromere.[9]
In the presence of a large concentration of yolk in the fertilized egg cell, the cell can undergo partial, or meroblastic, cleavage. Two major types of meroblastic cleavage arediscoidal andsuperficial.[citation needed]
| I. Holoblastic (complete) cleavage | II. Meroblastic (incomplete) cleavage |
|---|---|
A. Isolecithal (sparse, evenly distributed yolk)
B. Mesolecithal (moderate vegetal yolk disposition)
| A. Telolecithal (dense yolk throughout most of cell)
B. Centrolecithal (yolk in center of egg)
|
Compared to other fast developing animals, mammals have a slower rate of division that is between 12 and 24 hours. Initially synchronous, these cellular divisions progressively become more and more asynchronous. Zygotic transcription starts at the two-, four-, or eight-cell stage depending on the species (for example, mouse zygotic transcription begins towards the end of the zygote stage and becomes significant at the two-cell stage, whereas human embryos begin zygotic transcription at the eight-cell stage). Cleavage is holoblastic and rotational.
Inhuman embryonic development at the eight-cell stage, having undergone three cleavages the embryo starts to change shape as it develops into a morula and then ablastocyst. At the eight-cell stage theblastomeres are initially round, and only loosely adhered. With further division in the process of compaction the cells flatten onto one another.[13] At the 16–cell stage the compacted embryo is called amorula.[14][15] Once the embryo has divided into 16 cells, it begins to resemble amulberry, hence the name morula (Latin,morus:mulberry).[16] Concomitantly, they develop an inside-outpolarity that provides distinct characteristics and functions to their cell-cell and cell-medium interfaces.[17][18] As surface cells becomeepithelial, they begin to tightlyadhere asgap junctions are formed, andtight junctions are developed with the other blastomeres.[19][14] With further compaction the individual outer blastomeres, thetrophoblasts, become indistinguishable as they become organised into a thin sheet oftightly adheredepithelial cells. They are still enclosed within thezona pellucida. The morula is now watertight, to contain the fluid that the cells will later pump into the embryo to transform it into the blastocyst.
In humans, the morula enters theuterus after three or four days, and begins to take in fluid, assodium-potassium pumps on the trophoblasts pump sodium into the morula, drawing in water byosmosis from the maternal environment to becomeblastocoelic fluid. As a consequence to increased osmotic pressure, the accumulation of fluid raises the hydrostatic pressure inside the embryo.[20] Hydrostatic pressure breaks open cell-cell contacts within the embryo byhydraulic fracturing.[21] Initially dispersed in hundreds of water pockets throughout the embryo, the fluid collects into a single largecavity, called blastocoel, following a process akin toOstwald ripening.[21] Embryoblast cells also known as theinner cell mass form a compact mass of cells at theembryonic pole on one side of the cavity that will go on to produce the embryo proper. The embryo is now termed ablastocyst.[14][22] The trophoblasts will eventually give rise to the embryonic contribution to the placenta called thechorion.
A single cell can be removed from a pre-compaction eight-cell embryo and used forgenetic screening, and the embryo will recover.[23][24]
Differences exist between cleavage inplacental mammals and other mammals.