Cleavage (embryo)

In embryology, cleavage is the division of cells in the early embryo. The zygotes of many species undergo rapid cell cycles with no significant growth, producing a cluster of cells the same size as the original zygote. Depending mostly on the amount of yolk in the egg, the cleavage can be holoblastic (total or entire cleavage) or meroblastic (partial cleavage). The pole of the egg with the highest concentration of yolk is referred to as the vegetal pole while the opposite is referred to as the animal pole.

The end of cleavage coincides with the beginning of zygotic transcription. This point is referred to as the mid-blastula transition and appears to be controlled by the nuclear/cytoplasmic ratio (about 1/6). The different cells derived from cleavage (up to the blastula stage) are called blastomeres. A blastula is formed in many animals with a fluid-filled central cavity called a blastocoel.

Mechanism
The rapid cell cycles are facilitated by maintaining high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin dependent kinases (cdk). The complex CyclinB/cdc2 aka MPF (maturation promoting factor) promotes entry into mitosis.

The processes of karyokinesis (mitosis) and cytokinesis work together to result in cleavage. The mitotic apparatus is made up of a central spindle and polar asters made up of polymers of tubulin protein called microtubules. The asters are nucleated by centrosomes and the centrosomes are organized by centrioles brought into the egg by the sperm as basal bodies. Cytokinesis is mediated by the contractile ring made up of polymers of actin protein called microfilaments. 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.

Holoblastic
In the absence of a large concentration of yolk, four major cleavage types can be observed in isolecithal cells (cells with a small even distribution of yolk) or in mesolecithal cells (moderate amount of yolk in a gradient) - bilateral holoblastic, radial holoblastic, rotational holoblastic, and spiral holoblastic, cleavage. 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 cleavaging. 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.


 * Bilateral
 * 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
 * Radial cleavage is characteristic of the deuterostomes, which include some vertebrates and echinoderms, in which the spindle axes are parallel or at right angles to the polar axis of the oocyte.


 * Rotational
 * Mammals display rotational cleavage, and an isolecithal distribution of yolk (sparsely and evenly distributed). Because the cells have only a small amount of yolk, they require immediate implantation onto the uterine wall in order to receive nutrients.


 * 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.


 * Spiral
 * In spiral cleavage, the cleavage planes are oriented obliquely to the polar axis of the oocyte. At the third cleavage the halves are oblique to the polar axis and typically produce an upper quartet of smaller cells that come to be set between the furrows of the lower quartet.   All groups showing spiral cleavage are protostomia, such as annelids and mollusks.

Meroblastic
In the presence of a large amount of yolk in the fertilized egg cell, the cell can undergo partial, or meroblastic, cleavage. Two major types of meroblastic cleavage are discoidal and superficial.


 * Discoidal
 * In discoidal cleavage, the cleavage furrows do not penetrate the yolk. The embryo forms a disc of cells, called a blastodisc, on top of the yolk.  Discoidal cleavage is commonly found in birds, reptiles, and fish which have telolecithal egg cells (egg cells with the yolk concentrated at one end).


 * Superficial
 * In superficial cleavage, mitosis occurs but not cytokinesis, resulting in a polynuclear cell. With the yolk positioned in the center of the egg cell, the nuclei migrate to the periphery of the egg, and the plasma membrane grows inward, partitioning the nuclei into individual cells.  Superficial cleavage occurs in arthropods which have centrolecithal egg cells (egg cells with the yolk located in the center of the cell).

Mammals
There are several differences between the cleavage in mammals and the cleavage in other animals. Mammals have a slow rate of division that is between 12 and 24 hours. These cellular division are asynchronous. Zygotic transcription starts at the two, four, or eight-cell stage. Cleavage is holoblastic and rotational.

At the eight-cell stage, the embryo goes through a process called compaction. Most of the blastomeres in this stage become polarized and develop tight junctions with the other blastomeres. This process leads to the development of two different populations of cells: polar cells on the outside and apolar cells on the inside. The outer cells, called the trophoblast cells, secrete fluid on their basal (inner) surface to form a blastocoel cavity through the process of cavitation. These trophoblast cells will eventually give rise to the embryonic contribution to the placenta called the chorion. The inner cells adhere to one side of the cavity to form the inner cell mass (ICM) and will give rise to the embryo and some extraembryonic membranes. At this stage, the embryo is called a blastocyst.