If someone were to tell you that
cell death is a necessity in order for an embryo to develop properly, you may
think that they were crazy. This may
seem counterintuitive. It appears that
it would only make sense for cells to be continuously growing and dividing
during development, instead of killing themselves. However, programmed cell death, known as
apoptosis, is now recognized as not only normal, but as a requirement of proper
development.
Apoptosis
is one of the most common and well-known forms of cell death. It occurs when a cell loses its cohesion with
its neighboring cells, as well as with the extracellular matrix. The chromatin, which holds the genetic
information in the nucleus of the cell, condenses, fragmenting the DNA. A family of enzymes, known as caspases, break
down the cytoskeleton, which is responsible for giving the structural support
to the cell. Once the cell has gone
through all the morphological changes it will be consumed by phagocytes, which
eat up the cell’s remains.
It has been determined that the
death of cells is so closely regulated within a developing organism that it can
be very easily predicted. One of the
most studied vertebrate organisms for cell death is the chick. In an experiment performed by John Saunders, he
looked at cells that were destined to become part of the “posterior necrotic
zone,” located on the bud of a developing chick wing. It was found that when these cells were in
the chick embryo that they belonged to, they died right on schedule, even
though there was nothing damaged or diseased about them. However, when these cells were transplanted
to the backside of another chick, they would not go through apoptosis, but
instead would survive and differentiate.
During
organogenesis, perfectly timed cell death is responsible for coordinating the
development of organized cells into functional organs. It was found in 5 day old chick embryos that
apoptosis was key in the formation of the inner ear structure, as well as the
architecture of the four-chambered heart.
Additionally, it has been found that there are two apoptotic proteases,
enzymes that function to breakdown proteins, that are essential for normal
brain formation. These proteases have
been identified as caspase-3 and the Apoptosis Activating Factor apaf-1. Another structure that depends upon cell
death is the formation of the eye. As
the lens of the eye is forming, a partial apoptosis occurs, during which the
nuclei of the lens fiber fragment their DNA.
This eventually allows for the lens fibers to become transparent,
allowing us to see. Furthermore, we all
have dying cells to thank for our sex determination. The Sertoli cells within the testis secrete
the anti-Müllerian hormone, which causes the female ductal system to degenerate
in an embryo destined to become a male.
One important insight that has come
from this knowledge of cell death during development is a better understanding
into the consequences of teratogens and how they can lead to malformation in a
fetus. Additionally, it gives hope to
the possibility of finding a cure for cancer in the future. If researchers can learn as much as they can
about why certain cells will go through apoptosis and what signals determine
when it occurs, they can apply that knowledge to try and figure out why
homeostatic cell death sometimes fails to occur. With furthering research on this
ever-expanding topic, there can be new hope for cancer patients or for people
suffering form an autoimmune disease. Just
remember, even though the words “cell” and “death” in the same sentence may
seem alarming at first, apoptosis is a normal bodily process, and without it the
fascinating complex body would not be formed.
This image is an example of what would
happen if apoptosis was not working correctly.
The chromatin mentioned earlier in the post can also be seen in this
image.
Reference:
Zakeri,
Zahara, Carlos G. Penaloza, Kyle Smith, Yixia Ye, and Richard A. Lockshin.
"What Cell Death Does in Development." The International Journal
of Developmental Biology 59 (2015): 11-22. www.intjdevbiol.com. 22
May 2015. Web. 10 Oct. 2015.
Image Credit:
“Papillary Thyroid Carcinoma, FNA, Rapid Pap Stain” – Ed
Uthman; Flickr
This is a great read. Apoptosis functioning throughout the body is a perfect bridge from developmental biology research to medical applications in cancer and autoimmune disease prevention. It is also an example of how cells rely on both genetic and microenvironment signals for functions. I am curious to see the advances we make on this subject.
ReplyDeleteIt seems so ironic that cell death in the form of apoptosis is required for proper embryo development. How are the cells signaled to die? Why would those cells that are destined to die be generated in the first place? It seems like a lot of genetic waste and a misuse of energy. I found it very interesting how the cells that were transferred to the backside of the chicken survived and differentiated while those cells that stayed in the posterior neurotic zone died. Was it the location that triggered apoptosis or perhaps their function was no longer needed? It interesting how apoptosis plays a role in the development of different organs such as the eye, brain, and sex determination. If this research could eventually lead to curing cancer, everyone in the world would be affected because about 7.6 million people die of cancer globally per year (http://www.worldcancerday.org/world-cancer-day-2013-global-press-release). Image what other applications in medicine could be transformed if scientists and doctors could find a way to control cell death!
ReplyDeleteThe process of apoptosis is very intriguing and essential for proper development. Further knowledge about this process, as you state, is vital for developing cures to cancer. If there was a way to induce apoptosis in malignant cells, then the growth of the cancer could be inhibited. Also, apoptosis is a major process that occurs during the development of Fetal Alcohol Syndrome. Alcohol blocks glutamate receptors, causing widespread apoptotic neurodegeneration within the developing fetal brain. It is developmental abnormalities involving apoptosis like FAS that this research could have tremendous applications. It will be exciting to see where future research will go regarding this developmental cell death mechanism.
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ReplyDeleteApoptosis is a necessary process in many situations, such as degeneration of deformed cells or damaged cells, but it is interesting how it also plays a role in development as well.When we learned about Mullerian degeneration in class, I never attributed it to apoptosis, but now that makes perfect sense. It is thanks to Apoptosis that the bipotential development of reproductive structures is possible at all. I would be interested in knowing whether some widespread signalling molecules had something to do with the apoptosis of the necrotic zone on the chick, or whether it was induced by paracrine factors. In other words, if you put other cells (non necrotic zone cells) in place of the necrotic zone, would they undergo apoptosis in the same way?
ReplyDeleteI always understood that apoptosis was a required process in a plethora of cellular conditions; however, I was unaware how vital this 'programmed cell death' is in terms of development. It's very interesting to learn about how this cellular process can help develop potential treatments and cures for cancer. Although, 'cell death' may seem counter-intuitive at first, it is essential for normal cellular processes. I think Dan raises a good point above, in terms of whether or not signaling molecules play a heavy role in the process of apoptosis. I'm interested to see what further studies will show in terms of potential treatments for cancer and other malignant disease.
ReplyDeleteApoptosis is indeed an interesting concept, as it does go against the norms of thinking cells need to survive to create an organism. An interesting idea this brings up is the potential for incorrect regulation of apoptosis, and the results it may have on the fully developed organism. While the chick is studied in this specific article, it would be interesting to see the role apoptosis plays in xenopus eye development, as one of our tadpoles has only developed one eye. It would be interesting to know weather this was a result of an over-regulation of apoptosis, or a different root cause.
ReplyDeleteApoptosis is something that is vital in development. We would have webbed fingers and toes if apoptosis did not occur. I find it interesting that further study of apoptosis could help find solutions to cancer and autoimmune diseases. It is important to have a good balance of cell division and programmed cell death. Apoptosis is important in regulating cell division. Further studies could examine different model organisms and compare them with each other with the effects of apoptosis. Also, another study could be observing the difference between programmed cell death versus an outside factor causing cell death.
ReplyDeleteI think you did a really good job of thoroughly explaining apoptosis in general and in all its specific roles. You kind of hinted at one point that apoptosis may be related to the cell's specific location in the body which I found very intriguing. I would be interested to find out what exactly about the cell's environment or location that is causing this programmed cell death. I wrote my blog post about Mina J. Bissell and her theory that the microenvironment of a cell, like the extracellular matrix, provides certain context for the cell and I wonder if maybe this could also play a role in this planned apoptosis. Like others have said, the possible application of this with the treatment of cancer and other disorders could be life changing.
ReplyDeleteI typically think of apoptosis as the death of cells that have become damaged or diseased. It seems odd that there would be a systematic death of cells that are perfectly heathy, but it turns out that this process plays a crucial role in proper development. It makes sense when you think about it though. We are all initially female, but the presence of the Y chromosome triggers the female reproductive system to degrade. How else could this be carried out other than apoptosis? It is such a fascinating process that is vital not only in sex determination but also in numerous of developmental stages. This was a very interesting read that tied in a lot of information learned in class.
ReplyDeleteLike you mentioned, I always thought it was odd that certain cells would program their own death. Eventually, I learned more about the process of apoptosis and understood its implications. However, I never really knew how crucial apoptosis was in the development of certain organs. It is still surprising to learn about this and how it seems to be harmful to the organism but is actually very important and beneficial when it occurs as planned. It would be interesting to see what causes or prevents apoptosis in cases when it is not supposed to happen. Further research on this topic could potentially open up many doors in terms of treatments for the things you mentioned!
ReplyDeleteHello Laura,
ReplyDeleteI first would like to say that you did an awesome job with explaining this article and it was a very interesting read. I knew that cell death is important for regeneration of cells for other body functions, but I did not know that it is just as important for fetal development. However, it makes sense now. They have to get rid of the old to find a way for the new cells that they need in order to continuously grow! I wonder when apoptosis actually stops during the fetal development, or if its continuous until birth?
It is amazing that apoptosis is a part of embryo development and that cells often form important structures such as the heart and apoptosis is a major part of forming organs and playing a great role in proper development along with communication between neighboring cells. It is strange to think that cell death is necessary to further develop the embryo and then differentiate the cells to later be different organs and functions.
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