The process of regeneration was identified in the freshwater polyp Hydra almost 200 years ago.
However, it was previously unknown how the orderly regeneration of missing tissues or organs started the following damage.
An interdisciplinary research team at Heidelberg University was able to demonstrate how wound healing signals emitted after damage are translated into particular signals of pattern creation and cell differentiation by studying Hydra.
Mitogen-activated protein kinases (MAPK) and the Wnt signaling pathway are critical components that have stayed remarkably unaltered throughout evolution.
The healing ability of hydra polyps
LI FEI/Unsplash
Animals' capacity to repair varies greatly. Most mammals and vertebrates have limited regeneration potential, but early-evolving basic and simple creatures, such as cnidarians and planarians, can renew their whole body.
In all circumstances, the regeneration process begins with wound healing. Cells multiply and generate an undifferentiated mass - a blastema - from which the missing structures are re-patterned. This triggers genetic pathways that regulate embryonic growth.
To discover the molecular pathways involved, the research team led by Prof. Dr. Thomas W. Holstein researched the freshwater polyp Hydra to grasp the fundamental aspects of regeneration activation.
Anja Tursch's Ph.D. thesis lies at the heart of their studies. She replicated the critical experiment that led Geneva scientist Abraham Trembley (1710-1784) to discover the regeneration phenomena.
The Hydra polyp is split in half, causing the top half to regenerate a new "head" and the bottom half to regenerate a new "foot" thus, completely distinct body parts can develop from the same tissue at the cut area in the center.
The researchers at Heidelberg University's Centre for Organismal Studies (COS) have now demonstrated how this is feasible, building on their prior work on Hydra regeneration.
Any type of damage, regardless of where it happens, generates nonspecific signals for an injury response, such as wound healing, via calcium ions and the formation of reactive oxygen species.
Three mitogen-activated protein kinases, p38, JNKs, and ERK, transfer the signals intracellularly. Both head and foot regeneration require the activation of these three molecules.
Wnt signaling pathways are then activated, which are necessary for the creation of rudimentary organs and the body axis during embryonic development.
Thus, general wound healing signals are converted into position-specific patterning and cell differentiation signals for regeneration.
"Our findings reveal that the Wnt signaling pathway is a key component of the initial general injury response and, depending on signal amplitude, guides tissue toward head or foot growth," Prof. Holstein says.
This is why, in the case of MAPK inhibition, artificially created, recombinant Wnt proteins can cause regeneration that would otherwise be missing.
"It was also interesting that heads may be produced at both ends in intermediate body sections that had both head and foot removed," says Dr. Suat Ozbek, a member of Prof. Holstein's "Molecular Evolution and Genomics" research group at the COS.
Hydra is a genus of freshwater invertebrates in the Hydrozoa class (phylum Cnidaria). The body of such an organism is made up of a thin, generally transparent tube that may be up to 30 millimeters (1.2 inches) long but can contract significantly.
The body wall is made up of two layers of cells separated by the mesoglea, a thin, structureless layer of connective tissue, and the enteron, a hollow holding intestinal organs.
The bottom end of the body is sealed, while an aperture at the top ingests food and ejects waste. A cieeee of 4 to 25 tentacles surrounds this hole.
Individuals normally have different sexes, and eggs and sperm develop in separate swellings (gonads) in the outer body layer.
However, some species are hermaphroditic (i.e., functional reproductive organs of both sexes occur in the same individual).
Eggs are kept in the ovaries and fertilized by sperm from other people. Miniature hydras are finally released as offspring.
Budding is another method of vegetative reproduction. Finger-shaped outpushings of the wall grow mouths and tentacles before nipping off at the base to generate distinct new individuals.
Locomotion is accomplished by crawling on the adhesive base or looping; that is, tentacles adhere to the substrate, the base releases, and the entire body somersaults, allowing the base to attach to a new place.
The genus has roughly 25 species that differ mostly in color, tentacle length and number, and gonad location and size.
All Hydra species eat on crustaceans and other tiny invertebrates. Hydra is a unique hydrozoan genus in that it has no jellyfish stage and the polyp stage is solitary rather than colony.
