centrosome

ROBO-SPERM
SOURCE: Wellcome Images, B0007805 Sperm cell
Digital artwork/Computer graphic by Anna Tanczos

THE STRUCTURE OF A SPERM CELL
The male gamete

Each single spermatozoan (plural spermatozoa) contains a haploid number of chromosomes (one copy of each) in the nucleus situated in the head region.

Surrounding the head of the sperm cell is the acrosome cap [shown in blue] - this contains special enzymes that digest the zona pellucida (the membrane surrounding the egg cell) to assist in fertilization.

The mid piece of the sperm cell contains two centrosomes [in green] and coiled mitochondria [gold]. The sperm will contribute both centrosomes to the embryo upon fertilization, which are essential for organising microtubules and thus subsequent cell divisions of the embryo.

The large coiled mitochondria [gold] provide the sperm with the energy supplied to the long flagella (or tail) required for it motility.

The Embryo - Cleavage and Genetic Transition

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.

September 13th, 2013

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)].

Keep reading

Centrosomes and Cancer: Settling an Old Debate

Early last century, German biologist Theodor Boveri observed that cancer cells often harbor multiple copies of a cellular structure known as the centrosome. He was also the first to suggest that the extra centrosomes drive cancer. Researchers have since learned a great deal about the structure and many functions of Boveri’s “special organ of cell division.” But why cancer cells harbor multiple copies of this organelle — and whether they are “addicted” to having so many — has remained unanswered. So has the question of whether healthy human cells even require centrosomes to divide, making more cells. Now, 101 years after Boveri first aired his suspicions, researchers may have some answers.

A new study, published April 30 in Science, shows that while cancer cells are not addicted to multiple centrosomes, healthy cells absolutely require them to proceed with cell division. In the absence of centrosomes, healthy cells don’t divide, while malignant cells continue dividing and multiplying.

“Our results have settled a long-running debate in cell biology,” said co-senior author Karen Oegema, PhD, professor of cellular and molecular medicine at University of California, San Diego School of Medicine and member of the Ludwig Institute for Cancer Research. “Centrosomes make things so much better for healthy dividing cells, that cells have a protective mechanism that halts their division if they lose centrosomes.”

Ordinarily, the resting cell’s single centrosome serves as an organizing center for the cell’s skeleton. When a cell divides, however, the centrosome takes on another function. The centrosome duplicates and helps ensure chromosomes are distributed equally between the two daughter cells. Many cancer cells contain multiple centrosomes, and this error contributes to the misdistribution and abnormal numbers of chromosomes in daughter cells.

Still, it wasn’t clear that centrosomes are absolutely needed for cell division. Biologists have long known that other mechanisms exist to separate chromosomes. “The growing feeling among a number of cell biologists is that the centrosome is like the appendix of the cell,” said co-senior author Andrew Shiau, PhD, director of the Ludwig Institute’s Small Molecule Discovery Program in San Diego and visiting scientist at UC San Diego.

Earlier studies had sought to resolve the issue by cutting centrosomes out of cells or destroying them with lasers. But both normal and cancer cells treated this way simply remade their lost centrosomes, and then continued dividing.

To get around this limitation, in this study the researchers designed and synthesized a molecule that specifically and reversibly inhibits an enzyme named Plk4, which controls the assembly of centrioles — barrel-like protein structures from which centrosomes are made. They then showed that exposure to this inhibitor, called centrinone, eliminates centrosomes from both healthy cells and cancerous ones. When the compound was removed, cancer cells reverted to precisely the number of centrosomes they had before exposure to the molecule.

“This was in marked contrast to what normal cells would do when we persistently removed centrosomes,” Oegema said. “Normal cells arrested their growth when their centrosomes were absent. This suggests that they absolutely require centrosomes for division, which was not at all the thinking in the field.”

The researchers show that the pause in the division of healthy cells is governed by a protein named p53, which is mutated in about half of all cancers. Levels of p53 were elevated in cells treated with centrinone. When the protein was temporarily inactivated in normal cells, they too failed to arrest upon exposure to centrinone.

This new ability to reversibly eliminate centrosomes using centrinone is likely to benefit research in a wide variety of biomedical fields, given the organelle’s multiple roles — from organizing the cytoskeleton to sprouting hair-like structures known as cilia on certain cells. The findings might also have applications for cancer therapy, even if cancer cells aren’t addicted to centrosomes.

“The idea,” said Shiau, “is that you trigger p53 in normal cells and have them stop multiplying — and then introduce another agent that only kills continuously dividing cells.”

Researchers are now developing more drug-like variants of centrinone. Their goal is to identify combination cancer therapies that can be tested in clinical studies.

Pictured: Centrosomes (green nodes) gather at the poles of a cell as it prepares to divide