Regeneration inHydra
Authors: Galliot Brigitte 
Published: November 2013

Hydrafreshwater polyps have a remarkable ability to regenerate after bisection or even after dissociation, and thus offer a unique model system to investigate the cellular and molecular basis of eumetazoan regeneration. From a single cut along the body column two different types of regeneration arise: foot regeneration from the apical part and head regeneration from the basal part. The high proportion of stem cells in theHydrabody column supports these fast and efficient processes. Grafting experiments proved that the gastric tissue in the head‐regenerating tip rapidly develops ade novoorganising activity, as evidenced by the induction of an ectopic axis when transplanted onto a host. The molecular mechanisms involved in this transformation rely on the immediate activation of the mitogen activated protein kinase (MAPK) pathway and the subsequent activation of the canonical Wnt3 pathway. This early phase is followed by a patterning phase, when head regeneration requiresde novoneurogenesis.

Key Concepts:

Hydrais a bilayered freshwater solitary polyp that belongs to Cnidaria, a phylum that also includes jellyfish, sea anemones and corals. Cnidaria as sister group to bilaterians, belongs to Eumetazoa, that is, all animals that have a differentiated gut and nervous system.

Hydratissues contain three distinct stem cell populations that continuously cycle but cannot replace each other. The ectodermal and endodermal myoepithelial cells are differentiated cells that are also unipotent stem cells. These cells that cycle rather slowly provide all epithelial cells; however, these two lineages cannot replace each other. By contrast, the third lineage is multipotent, that is, the interstitial stem cells that cycle much faster (every 24–30 h) and provide nerve cells, nematocytes, gland cells as well as germinal cells.

Head regeneration requires a complex 3D reconstruction when foot regeneration appears much simpler, similar to tissue repair.

Head regeneration relies on a head organising activity that develops in several hours after bisection from the gastric tissue in the regenerating tip. This activity can be quantified at every time point of the regenerative process by lateral transplantation.

Successive waves of gene and protein regulations characterise each phase of head regeneration: immediate, early, early‐late and late. The immediate activation of the MAPK/RSK/CREB pathway followed by the early activation of the Wnt3 pathway participates in the establishment of the head organising activity.

After midgastric bisection, activation of the MAPK pathway leads to injury‐induced apoptosis of the interstitial cells, a cellular event that initiates head regeneration by activating the Wnt3 pathway in interstitial progenitors and subsequently in endodermal epithelial cells.

Head regeneration inHydrais highly plastic, as it is maintained, although at a slower pace, when cell cycling is transiently inhibited or slowed down in the early phase of head regeneration. This suggests that cell proliferation is not essential forHydraregeneration, at least during the early phase, a condition named morphallaxis.

Interstitial cycling cells play an important role at the early phase of head regeneration: those located at the tip receive signals from the apoptotic cells and rapidly divide, whereas those located more distantly migrate towards the wound. Both processes lead to the formation of a dense zone of progenitors in the regenerating tip.

Head regeneration inHydrais highly plastic, as it is maintained after elimination of the interstitial cell lineage, indicating that epithelial cells alone can drive the head regeneration process efficiently although with a significant delay.

Since 2002, transgenic strategies were successfully developed inHydra, allowing first the transient expression of reporter constructs, and since 2006 the establishment of stable transgenic lines.