Image credit: Melanie Worley (CC BY 4.0)

When regeneration goes awry

Fruit flies that mistakenly grow extra wings reveal a new regulator of plasticity during regeneration.


Some animals are more able to replace damaged tissue than others. A salamander, for example, can re-grow an amputated limb but a mouse or human cannot. After damage or injury certain types of cells are lost and need to be replaced by cells that are left behind. The remaining cells — or new cells that develop from them — must change their characteristics to better resemble the lost cells. This property, known as plasticity, needs to be controlled tightly. Excessive plasticity can result in forming tissues that are completely inappropriate for that location in the animal.

The fruit fly Drosophila melanogaster can be used to investigate plasticity during regeneration. Fruit fly larvae contain structures known as imaginal discs that can regenerate if damaged. Occasionally, when the imaginal discs regenerate, they produce the wrong kind of tissue.

Worley et al. set out to look for genes that would normally prevent such mistakes. Their search began with looking for flies with mutations that caused regeneration to go awry following damage. Specifically, Worley et al. looked for mutant flies that grew extra wings after a structure was damaged that would normally only generate a single wing. Once such flies had been found, further experiments were used to narrow down the search and confirm which gene was mutated.

This approach revealed that flies with mutations in the gene for a protein called CtBP (which is short for C-terminal binding protein) made more errors during regeneration and commonly regenerated inappropriate structures such as an extra wing. Importantly, mammals have very similar genes, but few researchers had previously studied if they also play a role in regeneration.

Worley et al. went on to show that CtBP dampens the activity of two signaling pathways (namely the JNK/AP-1 pathway and the JAK-STAT pathway), both of which promote plasticity. Thus, when CtBP levels are reduced, there is excessive plasticity.

These findings implicate CtBP as a regulator of plasticity during regeneration. This is an important first step in thinking of strategies that would allow researchers to guide and reshape the development of tissues during regeneration.

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