Wednesday, December 12, 2018

Speaking of Science: Regeneration superstars

Speaking of Science
Talk nerdy to us

The axolotl, also known as the Mexican salamander, shows a remarkable ability to regenerate nerves after damage. (Karen Echeverri/University of Minnesota)

The axolotl is a salamander that heals without scarring. It can regrow its limbs, jaw, skin and even parts of its brain and spinal cord. The salamander can regrow a severed arm dozens of times and always makes a perfect copy. These amphibians are, according to biologist Karen Echeverri, "the superstars of regeneration."

I saw dozens of axolotls last week at the Marine Biological Laboratory in Woods Hole, Mass., all of them pink and translucent. Frilly gills festoon the sides of their heads. (Native animals grow green-black skin in Mexico's streams, where they are endangered.) The translucent animals are a microscopist's dream.

Under magnification, using just a simple microscope, it is possible to see a salamander's three-chambered heart beat beneath its plastic-wrap skin. Echeverri and her colleagues have developed transgenic salamanders that are even more revealing. Cells in the salamanders' muscles, bloodstream and nervous system are tagged with a protein that glows green under fluorescent light.

The biologist showed me the regenerating tail of one of these gene-edited salamanders: Cells shuttled through blood vessels like commuters on their way to work. In the animal's tail, fresh spinal cells paved the way, laying a path followed by big cartilage scaffolds. Muscle fibers were just beginning to advance into the new limb.

"There is huge potential for human health," Echeverri said. Her goal is to come up with the "blueprint of pathways" that an axolotl's genes activate or repress during regeneration, and try to translate that pathway for humans. In particular, she's interested in regenerating skin; her recent work shows that the timing of when the salamanders deposit new collagen "is really important for whether you scar or don't scar." She's manipulating those same pathways in human cells in vitro.

Still, major questions remain. For instance: How do regenerating parts keep from growing into supersize limbs? Echeverri gestured with her arm, demonstrating regeneration gone amok. (I imagined an axolotl with the mutant elasticity of Mister Fantastic.) Echeverri doesn't know. Her see-through animals have yet to bare it all.


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