Boundary maintenance in the ancestral metazoan Hydra depends on histone acetylation.

Much of boundary formation during development remains to be understood, despite being a defining feature of many animal taxa. Axial patterning of Hydra, a member of the ancient phylum Cnidaria which diverged prior to the bilaterian radiation, involves a steady-state of production and loss of tissue, and is dependent on an organizer located in the upper part of the head. We show that the sharp boundary separating tissue in the body column from head and foot tissue depends on histone acetylation. Histone deacetylation disrupts the boundary by affecting numerous developmental genes including Wnt components and prevents stem cells from entering the position dependent differentiation program. Overall, our results suggest that reversible histone acetylation is an ancient regulatory mechanism for partitioning the body axis into domains with specific identity, which was present in the common ancestor of cnidarians and bilaterians, at least 600 million years ago.

FoxO is a critical regulator of stem cell maintenance in immortal Hydra.

Hydra's unlimited life span has long attracted attention from natural scientists. The reason for that phenomenon is the indefinite self-renewal capacity of its stem cells. The underlying molecular mechanisms have yet to be explored. Here, by comparing the transcriptomes of Hydra's stem cells followed by functional analysis using transgenic polyps, we identified the transcription factor forkhead box O (FoxO) as one of the critical drivers of this continuous self-renewal. foxO overexpression increased interstitial stem cell and progenitor cell proliferation and activated stem cell genes in terminally differentiated somatic cells. foxO down-regulation led to an increase in the number of terminally differentiated cells, resulting in a drastically reduced population growth rate. In addition, it caused down-regulation of stem cell genes and antimicrobial peptide (AMP) expression. These findings contribute to a molecular understanding of Hydra's immortality, indicate an evolutionarily conserved role of FoxO in controlling longevity from Hydra to humans, and have implications for understanding cellular aging.

Defining the origins of the NOD-like receptor system at the base of animal evolution.

Distinguishing self from nonself and the onset of defense effector mechanisms upon recognition of pathogens are essential for the survival of all life forms in the animal kingdom. The family of nucleotide -binding and oligomeriszation domain-like receptors (NLRs) was first identified in vertebrates and comprises a group of pivotal sensor protein of the innate immune system for microbial cell wall components or danger signals. Here, we provide first evidence that early diverging metazoans have large and complex NLR repertoires. The cnidarian NACHT/NB-ARC genes include novel combinations of domains, and the number of one specific type (NB-ARC and tetratricopeptide repeat containing) in Hydra is particularly large. We characterize the transcript structure and expression patterns of a selected HyNLR, HyNLR type 1 and describe putative interaction partners. In a heterologous expression system, we show induced proximity recruitment of an effector caspase (HyDD-Caspase) to the HyNLR type 1 protein upon oligomerization indicating a potential role of caspase activation downstream of NLR activation in Hydra. These results add substantially to our understanding of the ancestral innate immune repertoire as well as providing the first insights into putative cytoplasmic defense mechanisms at the base of animal evolution.