Shubin begins describing what he later names at ZRA on pg. 49 when he says "A strip of tissue at the extreme end of the limb bud is essential for all limb development. Remove it, and development stops. Remove it early, and we are left with only an upper arm, or a piece of an arm." I'm curious as to what further research has been done with this molecule. (Anyone up for looking for journal articles?) I suppose I would label this question a futuristic 'continuity and change' one, because what I'm curious about specifically, is the possibility of use for ZRA past the process of development. For example, if a person lost a finger or two (or an arm, or a leg, for that matter) in some sort of accident or war, would it be plausible to to somehow smear some ZRA on the spot to re-grow the digit/limb? Is this the future of biomedical engineering or just an idea for a cheesy science fiction movie? Would our genes even respond to this molecule or an undifferentiated stem cell past development?
(Jackie Edelson; jedelson92@gmail.com)
The strip of tissue that controls the development of limbs has its affect during the embryonic stage of animal development. The reason why it controls the outcome of limb development is because it is during the development and growth of the limbs. Therefore, the tissue cannot be applied after development because the limb won’t be growing anymore. Unless there is a method to stimulate the cells to turn on genes that will create limbs again, you cannot “smear” the tissue to regrow the limb or digit. Furthermore, there is some evidence that states that the ZPA doesn’t fully control the development of limbs but more of the position of the limbs. However, there is a possibility to use embryonic stem cells to build a limb for a war veteran or any person that has lost a limb. In theory, if the ZPA can be accepted by our genes and combined with the use of stem cells, then there is a possibility that we could regrow a limb. Technically, using the ZPA after development to regrow a limb or digit sounds almost impossible, but if it were possible there could be alternatives then directly applying the ZPA tissue. Shubin wrote in his book about the experiment by Randy Dahn that used the protein made by mouse Sonic hedgehog gene to influence the skeletal rod development in skates. Therefore, it doesn’t have to be the tissue that influences the development of limbs, but rather the protein that is translated from the Sonic hedgehog gene. Instead of using the tissue itself, we can just use the protein from mammals that are closely related to humans. This idea of using the tissue is still far off and, right now, it is more in the direction of a cheesy science fiction movie. The best choice right now is to use stem cells instead of this tissue.
ReplyDeletehttp://dev.biologists.org/content/50/1/217.full.pdf
Campbell book page 415
I agree with Benny and wish to expand on why it would not be possible to regrow a limb after it has been cut off.
ReplyDeleteFirst, only animals that can bud can replace limbs that have been severed. There are a few exceptions, like a sea star, but generally regrowing limbs is limited to Porifera and Cnidarians, like Hydra.
The reason a ZPA could not regrow limbs is because, like Benny said, it can only be activated during a specific phase in development. It's a block of mesodermal tissue that's located underneath the ectoderm where the posterior part of the bud is connected to the body. Dennis Summerbell and Lawrence Honig showed this in an experiment where they added an additional ZPA to a limb bud in a developing chicken. The chicken had twice as many digits and they were mirror images of the original, showing that ZPA cells secretes proteins that grow limbs and signal that the location is the posterior side (Campbell 1043).
Proteins that are transcription factors help control the rate at which a gene is transcribed. The limb bud expresses a transcription factor called ALX4 at the anterior part of the mesoderm, while the transcription factor HOXB8 being expressed at the posterior portion (This is a Hox gene). The Alx4 region, the medial region, and the HOXB8 expressing area meet at a proximal area where the AER develops. The ZPA forms where the Hox8 region joins the AER (Sauders and Gasseling 4). As a matter of fact, these regions are dependent on signaling in order for the appropriate events to occur. There are signals within the bud that stimulate the beginning of the release of Alx4 and other transcription factors. These are the Gli zinc-finger transcription factors, specifically Gli1, Gli2, and Gli3. Each are relased to stimulate the growing limb pathway (Todt and Fallon 3). The AER actually forms before the ZPA (Campbell 1044), so the AER must send these signals at exactly the right time to coordinate growth.
I disagree with Benny when he says that the proteins should be used to regrow limbs if possible. I think that embryonic stem cells should be used instead. I think that if one inserts the cells at the cut-off limb, and stimulates the cells with Alx4 and HOXB8 at the appropriate sites, then a limb could be regrown.
benitorosenberg12@comcast.net
http://www.ncbi.nlm.nih.gov/pubmed/9846378
http://www.ncbi.nlm.nih.gov/pubmed/3502993