The field of regenerative limb research is nowhere near as populated as some of the other biological sciences, like cancer research or stem cell research, but there is a fundamental importance to learning all we can from the creatures who possess this wonderful trait. Ed Yong wrote an awesome review of the subject some time ago on his blog “Not Exactly Rocket Science” which is definitely worth the read in order to gain some perspective on the entire field of regenerative research (and also definitely worth bookmarking in order to read some of the best reviews I have found on popular science).
One of the quotes from Ed’s article that really struck me at the time was, “[Ashley] Seifert doubts we will ever have an injectable cocktail of molecules that triggers regeneration.” I had a good chuckle then and again when I reread it this morning because that seemed exactly like the kind of quote that motivates a determined and tenacious scientist to overcome the odds and discover something miraculous. Of course, no one said science is easy, but this month a small group out of India may have discovered the first key ingredient for a regenerative cocktail.
Suresh Balakrishnan’s group worked with a common gecko called Hemidactylus flaviviridis, or the Yellow-bellied House Gecko. Like other geckos, it is readily able to discard its tail and grow a complete new tail, given enough time. (If you’d like to read an article about the intriguing mechanism of a gecko losing its tail in the first place, go to LiveScience.) Balakrishnan assumed that there must be several growth factors and receptors involved in the process of limb bud development, and it is also well known that FGF2 plays a critical role in epimorphosis from previous studies on salamanders and chick embryos. In order to further our understanding of vertebrate systems, they looked at gecko tail regeneration both in the presence or absence of an FGFR inhibitor, SU5402, a known tyrosine kinase inhibitor that would disrupt the FGF2-FGFR1 signaling pathway.
They tested 3 different stages of development with the inhibitor and found that FGF2 was quite important for early limb bud development. In fact, there was an inhibition of the formation of the wound epithelium as well as an inhibition of the formation of the blastema. But at later stages, once the blastema had already developed, there was little to no effect of the FGFR inhibitor on continued growth. Histological profiling of the tissue additionally showed retardation of mesenchymal cell differentiation, ependymal growth and blood vessel formation, all things known to be developmentally moderated by FGF2.
Of course, this isn’t the whole story. While Balakrishnan’s group saw a slowdown in bud formation and tail growth, it did still grow, if only at half the rate of a normal gecko. So there are likely multiple pathways that the cells can utilize to gain the same end goal, albeit not always equally. There is also the “small” question of which growth factors or chemicals contribute to the continued elongation of the cells after the point of limb bud formation when FGF2 stops being the big dog in the playground.
The interesting part of this kind of research to me isn’t the direct results on limb regeneration or whether humans may ever achieve that (I think we’re closer to using stem cell scaffolds and biological 3-D printers to get the same result!), but the other avenues that this research can lead, such as nerve regeneration for paraplegics or quadriplegics or perhaps even neural regeneration for stroke victims. The knowledge of how cells propagate and proliferate into organs is still a very mysterious process, but research such as this are slowly illuminating the pathway and dispelling the shadows of our understanding. One day soon, we will have that regenerative cocktail.
Pillai, A., Desai, I., & Balakrishnan, S. (2013). Pharmacological inhibition of fgfr1 signaling attenuates the progression of tail regeneration in the northern house gecko Hemidactylus flaviviridis. International Journal of LifeSciences Biotechnology & Pharma Research (2); Issue 4, pp. 263-278.
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