Eye of newt, and toe of frog: Organogenesis Imagine if complex structures like the eye could be regenerated to…

Eye of newt, and toe of frog: Organogenesis Imagine if complex structures like the eye could be regenerated to correct injury or birth defects.

Developmental biologists studying eye generation previously found a “cocktail of proteins” known as Eye Field Transcription Factors (EFTFs) that determine eye fate in the embryo by turning on precise patterns of gene expression. But is there an even more minimal set of instructions to induce an eye? Can an eye be formed anywhere on the body?

A new study finds that simple bioelectric signals, in the form of voltage gradients across the cell membrane, trigger eye development in the frog, Xenopus laevis . Early on, cells in the eye primordia become hyperpolarized, i.e., the charge difference, Vm, across the membrane is higher than that of neighboring cells. Locally depolarizing these cells blocked only eye development and disrupted the pattern of EFTFs without harming other organ development.

Next, researchers injected into the frog embryo various ion channels with predictable effects on the membrane voltage. Remember that ion channels move charged particles such as Na+ and K+ across the membrane to generate potential differences in the order of ~100 millivolts. Amazingly, they were able to induce eyes ectopically, all over the surface of the embryo. These artificially generated eyes had similar retinal cell arrangement as normal eyes.

Understanding eye development is the first step towards regenerative medicine. That would be good magic, better than the three witches of Macbeth could conjure:

“Eye of newt, and toe of frog,

Wool of bat, and tongue of dog,

Adder’s fork, and blind-worm’s sting,

Lizard’s leg, and owlet’s wing,—

For a charm of powerful trouble,

Like a hell-broth boil and bubble.”

This study, from Michael Levin’s group at Tufts University was just published online (Development 139, 313-323 (2012) doi:10.1242/dev.073759). Thanks to the awesome Rachel Maddow for showcasing this story: http://maddowblog.msnbc.msn.com/_news/2011/12/12/9368699-eye-of-frog-tail-of-worm

The Levin Lab website is pretty cool: http://www.drmichaellevin.org/research.html

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35 Responses to Eye of newt, and toe of frog: Organogenesis Imagine if complex structures like the eye could be regenerated to…

  1. Rajini Rao The bridge you create between Science and literature…is something to be admired..that is what I first saw in your post…now let me admire the Science in it…smiling

  2. Shruti Reddy says:

    Ions and cell membrane’s voltage is the key to regenerate an organ.. Wow this is fascinating !

  3. Posters like yourself make G+ worth my while. Thanks for sharing.

  4. Rajini Rao says:

    Why, thanks Nimble Vagrant ! Responses like yours make my day. 🙂

  5. Blake Caves says:

    I also enjoy your posts. They are definitely some of the most interesting inputs I have found.

  6. RJ Matlock says:

    Thanks for share, text and the 5 eyed toad…too real for school!

  7. Rajini Rao says:

    Ram K , not gene therapy per se although they do knock down or exogenously introduce genes in order to evaluate the effect of membrane voltage on eye development. The ectopic eyes are not innervated, I believe..but are morphologically differentiated into eye like structures.

  8. Rajini Rao says:

    Tony Bryson , lol, when my son was little, he actually believed that I had eyes at the back of my head. That didn’t last long, unfortunately, although I still try to stay one step ahead of his shennanigans.

  9. I am growing interest in one more branch of science! Thanks to your posts.

  10. I mean…these studies have been carried out right now all over the world and it might be interesting to see how advanced humans could go in regenerating complex organs like eyes…

  11. Great content in your posts Rajini Rao !

  12. Tom Lee says:

    Rajini Rao When I was in elementary school (second grade) there was this teacher who said he had a secret eye on the back of his head. He could see who was cheating on tests. We believed him then. From then on nobody in my class would cheat! lol. Another nice post, BTW!

  13. BRIAN DUPREE says:

    If the image ain’t being a fake or other medical damage, it’s a damn tricky disease, being transported by insects that are infected by certain type of parasites, it being spread by being stung as feeding on certain animals. The parasite damages as even re-programs the cell structures as cell growth, as the victims – frogs as mostly other small reptile animals may be able to be infected throughout of their entire life cycle – being artificially modified in such an way that the victim may survive as halfway may able to reproduce itself, but in a metical physical sense become crippled in such an way that it’s going to give an easy target for other predators, able to be stung as to be otherwise hunted easier, so that the parasite can ensure his own existents by being transported through the entire food chance of an certain food change/habitat, starting again by being stung by some animal that for example stings as feeds itself from others having the parasite within his body. The animal is being technically high-jacked for the existence of the parasite.

  14. BRIAN DUPREE says:

    sorry for my shitty explaination, as I’m being a bit tired as on a hurry…

  15. I am endorse Kershaw Rustomji. You have amazing skill to marry science and literature. I started looking forward for your posts…

  16. I think you are Great!!

  17. Innteresting in many sciences including…Political LOL

  18. DaFreak says:

    Rajini Rao Would you think that the eye is the only body part this works for or could you also grow ears, a liver or even hearts using this technique by applying different bioelectrical signals? oO

    Does this have anything to do with muscle tissue being formed after being electrically stimulated through those weird shaking workout machines? That it’s not the workout that creates more muscle but that this is just a result of the continuing electrical stimulation that happens when they are used? As usual, this is some pretty mindblowing stuff. It’s probably too early to say and perhaps the eye is just “easy”? I read somewhere about a lab in japan that grew a retina in a dish, using a completely different technique; http://www.nature.com/news/2011/110406/full/news.2011.215.html

    Stop sparking my interest in this stuff ><

    I need to drown in physics and shouldn’t have time for all this. :p

    On a sidenote, from that labsite; “If we knew what we were doing, it wouldn’t be called research, would it?” — Albert Einstein

    Gotta love uncle Albert. ^^

  19. Rajini Rao says:

    Koen De Paus , the Xenopus tadpoles are also famous for regeneration of complete tails, limbs and other craniofacial structures with similar underlying principles. The story in your link refers to the same “cocktail of transcription factors” that can program stem cells into the retina in a dish. The voltage changes in the article I posted precede the transcription factor programming, so they must represent a very early signal.

    I don’t know about this muscle workout machine (given my laziness, I’m willing to be on the receiving end of a few shocks to avoid working out!) but it seems plausible to me that electrical stimulation could alter muscle volume or at least tone. Biomedical engineers are doing amazing things with tissue/organ regeneration.

    I love that quote too..although I wish we knew what we were doing more often (than not). 🙂

  20. Julian Pardo says:

    Any way is a great Idea!!! And a pleasure to enjoy!!!

  21. Excellent…keep it up…

  22. Chimera!!!!!! Fascinating study. Bookmarked. I look forward to reading more of their research in the near future.

  23. Rajini Rao says:

    Shah Auckburaully , I have a ghostly heart regeneration story coming up, stay tuned 🙂

  24. You referenced HEART muscle, Do fat and extraneous tissues also grow, or does all that MUSCLE scrw them up. Stem cells are real mystery to me.

  25. Rajini Rao says:

    Stem cells can be coaxed to form any kind of tissue, including muscle, fat, etc.

  26. Wow!! HEART muscle is striated isn’t it? Iguess there are too many FAT cells if you have a heart attack huh?? Can METH cause a heart attack? If so, HOW??? Sorry I’m so stupid.

  27. Rajini Rao says:

    michael delaney Fat stored around the heart correlates with clogged arteries which block blood flow and cause a heart attack.

  28. daniel wyatt says:

    How many eyes are real?

  29. daniel wyatt says:

    By ‘normal’, I mean, do they connect to the brain-can the frog see thru any or all the eyes, other than the ones it would normally have?

  30. Rajini Rao says:

    daniel wyatt , good point: the ectopic eyes in the article I described are not enervated..they do not have the right neural connections. That would require more engineering, or the regenerated eyes could be induced in place of a damaged eye.

  31. daniel wyatt says:

    Thanks, saw my answer in your response to Ram K.

  32. Rajini Rao says:

    Here is an update on this exciting research from the Levin lab: they now have evidence that the ectopic eyes can actually sense light and that the animals can respond to it. Check out Chad Haney ‘s post on the news here: http://goo.gl/TJ50p

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