|
Regeneration and tissue repair are widely spread in the animal kingdom, actually present in most phyla although with surprisingly different efficiencies within a given phylum. Hydra, a freshwater cnidarian polyp, is a leader in this category as after amputation, this animal is able to regenerate any missing body part whatever its age. Moreover, it is now well established that most developmental genes active in vertebrates do have counterparts in cnidarians. Hydra therefore provides a unique model system to investigate the cellular remodeling and the genetic circuitry required to regrow a complex structure as a hydra head from a gastric tissue. Gene silencing is a loss-of-function assay that demonstrates the function of a given gene for a given biological process. In the recent years, our laboratory was able to adapt to hydra a method whereby gene expression could be specifically knocked down through RNA interference, the animals being fed with double-stranded RNAs (Chera, de Rosa et al., J. Cell Science, 2006). By carefully selecting a subset of genes with potential involvement in regeneration we have been able to reveal some key cellular processes and regulators of head regeneration. We showed that some protease inhibitors are definitely required to promote cell survival and allow the animals to survive the amputation stress. When silenced, the gland and intestine cells display a massive autophagy (cell death through self-digestion). Interestingly, the same inhibitors likely play a similar role during pancreatic regeneration in mammals, and lead to chronic pancreatitis through autophagy when deficient in mice and humans (Galliot, Authophagy, 2006). For the first time, this approach showed that related molecules provide similar cellular phenotypes from hydra to mammals. By using the same approach but targeted against a highly conserved homeobox gene (Gsx/Cnox-2), we could establish that de novo proliferation of neuronal progenitors is required at the time a new head forms in the regenerating tip (Miljkovic-Licina et al., Development, 2007). Interestingly, the related genes in mouse and Drosophila also regulate neurogenesis. Hence, hydra regeneration relies on spatially-restricted and timely-orchestrated cellular modifications that are regulated by a set of highly evolutionarily conserved genes (Galliot et al., Sem Cell Dev Biol, 2006). Therefore we anticipate that the silencing of hydra regeneration specific genes will give us more clues not only about cnidarian regeneration, but also about the core mechanisms regulating stem cells and cell plasticity in regenerative processes in general.
|