Temperature and insulin signaling regulate body size in Hydra by the Wnt and TGF-beta pathways.

How multicellular organisms assess and control their size is a fundamental question in biology, yet the molecular and genetic mechanisms that control organ or organism size remain largely unsolved. The freshwater polyp Hydra demonstrates a high capacity to adapt its body size to different temperatures. Here we identify the molecular mechanisms controlling this phenotypic plasticity and show that temperature-induced cell number changes are controlled by Wnt- and TGF-ß signaling. Further we show that insulin-like peptide receptor (INSR) and forkhead box protein O (FoxO) are important genetic drivers of size determination controlling the same developmental regulators. Thus, environmental and genetic factors directly affect developmental mechanisms in which cell number is the strongest determinant of body size. These findings identify the basic mechanisms as to how size is regulated on an organismic level and how phenotypic plasticity is integrated into conserved developmental pathways in an evolutionary informative model organism.

Rethinking the Role of the Nervous System: Lessons From the Hydra Holobiont.

Here we evaluate our current understanding of the function of the nervous system in Hydra, a non-bilaterian animal which is among the first metazoans that contain neurons. We highlight growing evidence that the nervous system, with its rich repertoire of neuropeptides, is involved in controlling resident beneficial microbes. We also review observations that indicate that microbes affect the animal's behavior by directly interfering with neuronal receptors. These findings provide new insight into the original role of the nervous system, and suggest that it emerged to orchestrate multiple functions including host-microbiome interactions. The excitement of future research in the Hydra model now relies on uncovering the common rules and principles that govern the interaction between neurons and microbes and the extent to which such laws might apply to other and more complex organisms.

Stem Cell Transcription Factor FoxO Controls Microbiome Resilience in Hydra.

The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.

Blood system formation in the urochordate Ciona intestinalis requires the variable receptor vCRL1.

Adaptive immune systems are present only in vertebrates. How do all the remaining animals withstand continuous attacks of permanently evolving pathogens? Even in the absence of adaptive immunity, every organism must be able to unambiguously distinguish "self" cells from any imaginable "nonself." Here, we analyzed the function of highly polymorphic gene vCRL1, which is expressed in follicle and blood cells of Ciona intestinalis, pointing to possible recognition roles either during fertilization or in immune reactions. By using segregation analysis, we demonstrate that vCRL1 locus is not involved in the control of self-sterility. Interestingly, genetic knockdown of vCRL1 in all tissues or specifically in hemocytes results in a drastic developmental arrest during metamorphosis exactly when blood system formation in Ciona normally occurs. Our data demonstrate that vCRL1 gene might be essential for the establishment of a functional blood system in Ciona. Presumably, presence of the vCRL1 receptor on the surface of blood cells renders them as self, whereas any cell lacking it is referred to as nonself and will be consequently destroyed. We propose that individual-specific receptor vCRL1 might be utilized to facilitate somatic self/nonself discrimination.

Development of immunoreagents for diagnostics of CagA-positive Helicobacter pylori infections.

BACKGROUND: Helicobacter pylori strains expressing cytotoxic CagA protein are more likely to provoke severe gastric mucosal pathology and cause adenocarcinoma development than that lacking CagA. Determination of the CagA-status of a pathogen, therefore, is regarded as informative approach in H. pylori infection diagnostics and disease risk prediction. MATERIALS AND METHODS: Molecular cloning, recombinant protein expression in Escherichia coli, affinity chromatography, electrophoresis and commonly used techniques of hybridoma production and screening were used as well as different immunosorbent assays and Western blot procedures. RESULTS: Four overlapping N-terminally His(6)-tagged recombinant fragments of CagA that covered the entire CagA sequence were produced and purified. An ELISA for specific anti-CagA serum antibodies detection was developed and evaluated. Utilizing recombinant fragments, the first set of monoclonal antibodies against CagA-antigen was produced and characterized. Three antibodies recognized distinct linear epitopes inside conserved regions of the cytotoxin whereas the epitope of the forth antibody was mapped in the variable area of CagA. The monoclonal antibodies allowed discriminating CagA-positive and CagA-negative H. pylori strains by means of Western blot and immunosorbent assays. CONCLUSIONS: The use of recombinant protein technology allowed obtaining pure CagA antigen, thus providing new perspectives for development of immunodiagnostic reagents. The set of monoclonal antibodies is a valuable tool for determination of CagA-status of H. pylori infection and for the investigation of cytotoxin molecule as well.