Dynamics of Tissue Patterning in Hydra

In this work we explored regeneration and homeostatic body patterning of the simple cnidarian Hydra. Thanks to its evolutionary position, this animal is well suited to identify cellular and molecular mechanisms of tissue organization conserved among metazoans.
In the first part, we used regenerating Hydra tissue spheroids as a model for understanding how mechanical signals affect cellular self-organization and tissue patterning. In this system, the specification of missing body parts is accompanied by tissue stretching generated through periodic osmotically driven inflation and deflation cycles. However, their role in regeneration was not known. We found that these oscillations are not only accompanying but required for successful symmetry breaking and regeneration. The data also indicated that the cellular readout is continuous rather than cyclic as the spheroids did not seem to have a mechanism for counting the oscillations. We identified this readout to be the transcription of a key organizer-defining factor Wnt3, which is quantitatively related to the overall amount of tissue stretching experienced by the spheroid. Moreover, when supplied externally, Wnt3 enables successful regeneration without mechanical stimulation. Beyond elucidating the role of mechanical oscillations for Hydra regeneration, the work points out a potentially conserved mechanism for translating mechanical stretching into chemical signals. Since tissue stretching also triggers the expression of Wnt ligands in various developmental contexts in vertebrates, it can represent a conserved feature of this signaling pathway.
The second part used unbiased approaches to identify factors downstream of the Wnt organizer, regulating the differentiated cell identities. This led to the discovery of a conserved zinc-finger transcription factor Zic4 to be a crucial cell fate regulator in Hydra. Upon its knockdown, tentacle battery cells transdifferentiate to the basal disk cells, likely in a cell-cycle dependent manner. These findings suggested a possible general framework for the connection of fate specification and axial position of epithelial cells in the Hydra body. We also explored new strategies to find new small molecules, such as metabolites, involved in patterning and discuss one putative example.