Generic and context-dependent gene modulations during<i>Hydra</i>whole body regeneration

<jats:title>Abstract</jats:title><jats:p>The cnidarian<jats:italic>Hydra</jats:italic>is a classical model of whole-body regeneration. Historically,<jats:italic>Hydra</jats:italic>apical regeneration has received more attention than its basal counterpart, most studies considering these two regenerative processes independently. We present here a transcriptome-wide comparative analysis of apical and basal regeneration after decapitation and mid-gastric bisection, augmented with a characterization of positional and cell-type expression patterns in non-regenerating animals. The profiles of 25’637<jats:italic>Hydra</jats:italic>transcripts are available on HydrATLAS (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://hydratlas.unige.ch">https://hydratlas.unige.ch</jats:ext-link>), a web interface allowing a convenient access to each transcript profile. These data indicate that generic impulse-type modulations occur during the first four hours post-amputation, consistent with a similar integration of injury-related cues on both sides of the amputation plane. Initial divergences in gene regulations are observed in regenerating tips between four and eight hours post-amputation, followed by a dramatic transcriptomic reprogramming between eight and 16 hours when regulations become sustained. As expected, central components of apical patterning,<jats:italic>Wnt3</jats:italic>and<jats:italic>HyBra1</jats:italic>, are among the earliest genes up-regulated during apical regeneration. During early basal regeneration, a BMP signaling ligand (<jats:italic>BMP5-8c</jats:italic>) and a potential BMP inhibitor (<jats:italic>NBL1)</jats:italic>are up-regulated, suggesting that BMP signaling is involved in the basal organizer, as supported by higher levels of phosphorylated Smad in the basal region and by the LiCl-induced extension of<jats:italic>NBL1</jats:italic>expression. By contrast, upon ectopic activation of Wnt/β-catenin signaling,<jats:italic>NBL1</jats:italic>is no longer expressed, basal differentiation is not maintained and basal regeneration is abolished. A tight cross-talk between Wnt/β-catenin apically and BMP signaling basally appears necessary for maintaining and regenerating<jats:italic>Hydra</jats:italic>anatomy.</jats:p>