Switching ON and OFF the Wnt/?-catenin pathway in Hydra vulgaris.

Signalling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator ?-catenin (?-cat) is one of the fundamental mechanisms that direct cell proliferation, cell polarity, and cell fate determination during embryonic development and tissue homeostasis in all metazoan organism, from Hydra to mammals. As expected, inappropriate activation of the Wnt pathway is implicated in a variety of human birth defects, cancers, and other diseases, and as consequence the modulation of this pathway at several levels might have profound therapeutic benefits both in regenerative medicine and anti cancer strategies. To this aim, we studied in Hydra the effect of switching OFF and ON the Wnt/?-cat pathway, by employing molecular approaches and novel drug delivery systems acting at transcriptional and protein levels, respectively. Switch OFF the Wnt signalling was achieved by downregulation of ?-cat mRNA expression levels by siRNA mediated RNAi. Interfered animals presented a higher number of nematoblast nests with respect to wild-type animals and overexpressed the nematoblast-specific marker nb035. Interestingly, they showed a delay in ectopic tentacle formation upon activation of Wnt pathway mediated by alsterpaullone (ALP). An advanced switching ON strategy of Wnt signalling was achieved by mean of optically addressable microcapsules loaded by ALP. NIR triggered delivery of ALP induced forced activation of Wnt/?-cat pathway, suggesting the possibility to remotely manipulate Wnt pathway in a few cells. Results obtained in Hydra may open the path to the more ambitious goal to achieve spatio-temporal control of stem cell fate for tissue healing/regeneration strategies in higher organisms.