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21 June 2009 No Comment

Genetic ablation system to study regeneration in Drosophila

Researchers have always puzzled for ages over how some animals can regenerate their lost or damaged body parts. It all began way back in 1740 when Swiss researcher Abraham Trembley observed that hydra-when chopped into two pieces could remarkably grow back into two complete, new organisms. However not all animals have same capacity of regeneration , for instance the planarians (flat worms) can be cut into 50 pieces and you will end up with 50 smaller worms and same can be said about beautiful star fishes, If an arm of a starfish is cut off, you will have two starfish after regeneration. Regeneration is quite common among invertebrates and they show tremendous ability to regenerate parts like legs or entire sections of the body when compared to vertebrates. There is only one group of vertebrate that has the capacity to regenerate highly complex structures such as limbs, jaws, tail, spinal cord, or eyes throughout their lives: the urodele amphibians. Humans also exhibit limited power of regeneration , for example a part of liver removed during surgery can be regained to the original size. Researchers have found that when properly enticed, some types of specialized human cells can revert to a more nascent state as observed in the case of our blood, skin, and bones where stem cells helps in replenishing.
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To understand properly the mysteries of regeneration will largely depend on the ability in understanding what mechanisms separates our wound-healing process from that of animals that are able to regenerate. The study of regeneration was hampered by lack of proper model systems but things are getting better as evident by studies in planiaria and zebra fish. Taking a step further Iswar Hariharan’s lab introduce a genetic ablation system in Drosophila melanogaster with the potential for large-scale identification of new regulators of regeneration and might help to studying regeneration at molecular level. In the latest issue of developmental cell Smith-Bolton and colleagues describe a new unbiased method for identifying regulators of regeneration. It is pretty well known that adult Drosophila are incapable of regenerating damaged appendages, however Hadorn and Buck in 1962 showed that Drosophila imaginal discs, the larval primordia of adult structures such as the wing and leg, are indeed capable of undergoing regenerative growth when implanted into the abdomens of adult females.

A related phenomenon termed transdetermination is also observed in imaginal discs where disc cells switch identity;e.g., wing cells to leg cells. However the mechanisms are different when compared to that involved in regeneration and difficulties associated with transplantation techniques have always hindered high-throughput examination of imaginal disc regeneration. This new technique from Hariharan’s lab using genetic tools offers an excellent way to study mechanism of regeneration. The authors used classical UAS-GAL4 system in association with Gal80 to express Eiger or Reaper to induce apoptosis. By performing some very elegant experiments have shown that tissue damage leads to loss of markers of cell fate commitment and expression of patterning genes were also altered. This is accompanied by induction of wingless and Myc , which are pivotal for regenerative growth. Finally authors demonstrate that ectopic activation of Myx enhances regeneration but as the animal grows older the ability to regenerate is lost and cannot be restored by activation of Wingless or Myc. This new system provides an excellent tool for unbiased forward genetic screen in order to search for regulators of regeneration.

Reference:

Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc.
Smith-Bolton RK, Worley MI, Kanda H, Hariharan IK.
Dev Cell. 2009 Jun;16(6):797-809.

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