Molecular signature of an ancient organizer regulated by Wnt/β-catenin signalling during primary body axis patterning in Hydra

Abstract

Wnt/β-catenin signalling has been shown to play a critical role during head organizer formation in Hydra. Here, we characterized the Wnt signalling regulatory network involved in formation of the head organizer. We found that Wnt signalling regulates genes that are important in tissue morphogenesis. We identified that majority of transcription factors (TFs) regulated by Wnt/β-catenin signalling belong to the homeodomain and forkhead families. Silencing of Margin, one of the Wnt regulated homeodomain TFs, results in loss of the ectopic tentacle phenotype typically seen upon activation of Wnt signalling. Furthermore, we show that the Margin promoter is directly bound and regulated by β-catenin. Ectopic expression of Margin in zebrafish embryos results in body axis abnormalities suggesting that Margin plays a role in axis patterning. Our findings suggest that homeobox TFs came under the regulatory umbrella of Wnt/β-catenin signalling presumably resulting in the evolution of primary body axis in animal phyla.

Epigenomic landscape of enhancer elements during Hydra head organizer formation

“…Following MEME-ChIP, the obtained motifs were submitted to TOMTOM in MEME-Suite to identify the TF that binds to the intergenic region. RNA-seq data generated previously in the lab [19] was used to show transcription over the selected peak regions (SAMN08966965).…”

“…This makes Hydra an ideal model system to study the process of axis patterning where the primary longitudinal axis is the oral-aboral axis. We have identified the downstream molecular players of the Wnt/β-catenin signaling pathway which resulted in the identification of multiple homeobox transcription factors that play a critical role in Hydra axis formation [19].…”

“…Studying enhancers in the process of axis patterning is critical to understand the mechanisms through which the various signaling processes operate. In Hydra the process of axis patterning is also recapitulated during the process of regeneration [ 19 , 29 ]. During this process, rapid and large-scale alterations in gene expression take place and these require changes in the chromatin architecture regulated by epigenetic modifications and regulatory regions in the genome [ 30 , 31 ].…”

Bacteria- and temperature-regulated peptides modulate β-catenin signaling in Hydra

“…Until now, it is unclear how Eco peptides antagonize the Wnt pathway, but we assume that they act downstream of β-catenin, given the following arguments. First, we showed that Eco-KD animals have a higher probability of forming tentacles after ALP treatment but have normal regeneration capability; thus, Rax could be a target transcription factor inhibited upon Eco signaling (67). Secondly, we showed that low temperature is antagonizing the effect of overexpressed β-catenin.…”

“…But none of them seem to resemble all assumed properties of the HI in the Gierer–Meinhardt model. Further, several downstream genes of the Wnt-signaling pathway have been shown to be involved in specific aspects of Wnt signaling: For example, the homeobox gene rax is important for tentacle formation ( 67 ), PKC signaling seems to be important for head regeneration ( 68 ), but not in bud formation ( 69 ), while ERK signaling was essential for both processes ( 68 , 69 ). We thus argue that several levels of Wnt inhibition exist and that the activity of Eco peptides provides one mechanism.…”