Axolotls (Ambystoma mexicanum) are a species of tiger salamander that used to populate the lake on which Mexico City grew. Grown ups commonly measure 23 cm (9 inches) in length. Axolotls are distinct from other amphibians in that they usually do not undergo metamorphosis. Although the salamanders develop lungs, most reach adulthood without shedding their external gills and retain an aquatic lifestyle, using both sets of organs to breathe. The preservation of juvenile traits is known as neoteny.
In my post dated Jun. 23, 2008, I have written about a hormone produced in the brain that seasonally alters hamster behavior and physiology. More dramatically, another brain hormone profoundly alters the axolotls' gross anatomy. That is, the administration of thyroid stimulating hormone (TSH), a hormone excreted by the pituitary gland, overcomes neoteny, inducing metamorphosis into a terrestrial salamander without gills. TSH stimulates the production of thyroxine in the thyroid. Iodine is a component of thyroxine. Therefore, adding thyroxine or iodine to the water also triggers metamorphosis. Dwindling water levels are thought to increase TSH production, inducing the transformation naturally. As consequence, two distinct, mature life forms of the same species may coexist.
In addition to the capacity to profoundly adapt to a change in the environment, axolotls exhibit an astounding ability of limb restoration after injury. The tissue surrounding the wound does not scar. Instead, the salamanders can regenerate a fully functional new limb within weeks after the loss. Recent research shows that the skin cells do not revert into pluripotent undifferentiated stem cells (Kragl and others, 2009). Rather, remnant cells from each tissue of the limb collectively form clusters, known as blastema. The blastema cells are more restricted in their potential than stem cells, constituting progenitors predestined to redevelop the components of the limb. The whole process seems to unfold like an intricate, precise molecular machinery that completes its mission according to plan without fail, once the cog is pulled. A timed, sweeping cascade of molecular signaling pathways switches the expression of genes, the product of which control the expression of other genes, resulting in orderly, topographic cell division and differentiation. Unraveling the molecular signals that set these processes in motion may lead to great advances in regenerative medicine.
In accord with the axolotls' striking capacity to fully regenerate limbs, the animals show a high degree of brain plasticity. I saw the otherworldly creatures close up for the first time, when I visited a friend working on his thesis in another laboratory at my alma mater. His professor had accomplished to produce fully functional axolotls with an additional vestibular system, successfully grafting in embryos heads with the premordia for the vestibular system onto bodies with another set of vestibular premordia (Brändle, 1977). The vestibular system endows the animals with a sense of balance and motion. In some animals, sensory nerve cells in the added vestibular system had grown connections intermeshed with those of the other vestibular system, providing sensory input to the processing stations of the vestibular pathway in the brain. The professor examined how the additional input affected the salamanders' reaction to rotation. He observed that the operated salamanders responded significantly more vigorously to rotation than unoperated salamanders. Apparently, the added vestibular nerve fibers he observed in histological preparations found appropriate targets in the brain and the information they conveyed was successfully integrated in the sensory pathway, translating into action proportionate to the enhanced input. Hence, axolotls constitute impressive examples for the formidable potential of vertebrates not only to repair themselves, but also to reorganize the nerve cell networks in their central nervous system according to a modified sensory periphery.
The video shows axolotls that had the genes for green fluorescent protein (GFP) inserted into their genome. Kragl and others, (2009) used similar labeling techniques to distinguish among blastema cells. I wrote about Douglas Prasher who cloned and sequenced GFP, making this video possible, in my post dated Oct. 23, 2008. Enjoy the show:
Addendum
- The Italian scientist Lazzaro Spallanzani was the first to report the salamander's ability of regenerating a limb, succeeding in regrowing tails (Spallanzani, 1768; for review in English see Tsonis and Fox, 2009). He also was the first to suggest that small bats must posses an extraordinary sense of orientation different from vision, known as echolocation today. I wrote about the controversy this idea stirred in his day in post with the entitle "Echolocation, Science & Power" published Sep. 3, 2009 (10/14/10).
- Brändle K (1977) Quantitive studies of the reactions to horizontal angular accelerations in axolotls. II. head-turning reflexes in animals with a supernumerary pair of labyrinths. J Exp Biol 66:15-31.
- Spallanzani L (1768) Prodromo di un opera da imprimersi sopra la riproduzioni anamali. Giovanni Montanari, Modena. Translated in English by Maty M. 1769. An essay on animal reproduction. London: T. Becket & DeHondt.
- Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460:60-65.
- Tsonis PA, Fox TP (2009) Regeneration according to Spallanzani. Dev Dyn 238:2357-2363.
No comments:
Post a Comment