The Embryo — Cleavage and Genetic Transition -

Philip Iannaccone
4 min readSep 4, 2018

On the left: Image of the mitotic spindle in a human cell showing microtubules in green, chromosomes (DNA) in blue, and kinetochores in red. On the right: Gli1 protein expression labeled in green, DNA labeled red. Gli1 is shown bound to the microtubules during cell division (image courtesy of the Iannaccone Lab, Lurie Children’s Research Center). Nucleus diameters are approximately 10µm, or about four 100,000ths of an inch.

Mom’s genes load proteins and RNAs into the oocyte and control DNA replication in the one-cell zygote as well as the first cleavage which leads to the two-cell stage. The two-cell stage is where the mouse embryo switches from being controlled by maternal genes to being controlled by the embryo’s genome. In humans this transition happens at the 4–8 cell stage. This changing of the guard is where exclusive expression of genes from Mom prior to fertilization transition to expression of genes from the new embryo. Genes that are now uniquely the product of fertilization.

In other mammals the change in control varies from the 8-cell stage to the 16-cell stage called morulae [pronounced “more-you-lee” and the plural of morula]. Derived from the Latin for mulberries because the morulae are clumps of cells that sort of resemble mulberries.

On the left: Mulberries (adapted from the 1911 Encyclopædia Britannica). On the right: Two rat morulae at the 8-cell stage — morulae are 100 µm in diameter, or about four 10,000ths of an inch (image courtesy of Greg Taborn, Lurie Children’s Research Center).

One example of this shift is RNA polymerase II. The activity of RNA polymerase II has not been found in the one-cell zygote, while it is present in two-cell embryos. [RNA polymerase II is an enzyme (a protein that makes chemical reactions go faster) which is the main machine for turning the genetic code in our DNA into RNA that directs the production of specific proteins (see our previous post Genes, DNA, and RNA)].

The cleaving embryo is held in the zona pellucida (a clear structure that is our version of an egg shell) which prevents it from adhering to the oviduct wall. Cleavage in mammals is a relatively slow process, varying from 12 to 24 hours after fertilization. The time elapsing between the first and second cleavages is variable. Successive cleavages occur after shorter and shorter intervals and become asynchronous. The first cleavage produces two cells and begins in the ampulla of the oviduct, the second cleavage to produce four cells occurs about 2 days following fertilization, the third to produce eight cells about 3 days after fertilization.

During the first cleavage the chromatin contents of the two pronuclei combine with each other to form the nucleus of each of the cells. The amount of DNA in each nucleus doubles before each division, and RNA and protein synthesis is enhanced significantly during cleavage. The sperm provides important machinery for proper combination of chromosomes from Mom and Dad. A structure called the centrosome (an essential structure for cell division) lines up another structure called the aster that comprises little cables that radiate like spokes on a wheel from an attachment point on each of the chromosomes (the kinetochore). This complex then pulls the correct chromosomes into each of the daughter cells as the cell divides. This amazing process also provides some of the prettiest pictures in cell biology and is the header image at the top of this post.

The dividing embryo moves through the oviduct as a result of ciliary motion of the oviductal epithelium. Meaning that the cells lining the inside of the tube, the oviductal epithelium, have little hair like structures, called cilia, that move in concert in one direction to push the embryo along. Also helping move the embryo along is muscular motion of the wall of the oviduct. These cleavages continue as the embryo makes its way along to the uterus, the site of implantation.

A review:

  • When a sperm cell from Dad inserts into Mom’s egg (fertilization) the egg divides into two cells within 12–24 hours.
  • The product of fertilization is called a zygote and it develops into an embryo following a plan laid out by Mom. Protein and RNA from Mom are preloaded into the egg before fertilization
  • The individual cells in the zygote are called blastomeres and from 2 cells we became 4 cells and then 8 cells.
  • Sometime before there are 8 cells genes unique to the embryo are activated. These genes are the baby’s genes and continue the developmental plan.
  • The cell divisions don’t occur at the same time and the DNA in each nucleus has to copy itself before the division.
  • The chromosomes must be shared accurately (divided evenly) between the cells that result from the division. If they are not either the embryo dies or bad congenital diseases like Down Syndrome occur.
  • All these events occur as the embryo is pushed inexorably down the oviduct toward the uterus where it will implant and grow into a baby.

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Originally published at lcresearchcenter.tumblr.com.

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Philip Iannaccone

Phil Iannaccone is a Professor of Pediatrics and Pathology at Northwestern University Feinberg School of Medicine.