Hydra: an out-groupmoves toward thecenterAdam S. Wilkins

Superficially, it might seem that Hydra has a rather che-quered history as an experimental subject. During thescramble to find new animal model systems in the 1960sand ‘70s, this simple cnidarian was one of the first to yieldnew insights into developmental mechanisms. In particular,the influential ideas about pattern formation that were de-veloped by Alfred Gierer and Hans Meinhardt were elabo-rated in conjunction with experimental work on Hydra. Yet,as more genetically tractable model systems came onstream Hydra experienced a partial eclipse. Today, however,the cnidarians have acquired a new importance: these ani-mals constitute the closest out-group to the triploblasticmetazoans. If one wants to understand the origins of bilat-erally-symmetric, triploblastic metazoans, it is essential tounderstand the molecular and genetic bases of develop-ment in these radially symmetric, diploblastic animals. Be-tween September 20th and 23rd, 118 participants gatheredat Tutzing, Germany, for the 8th International Workshop onHydroid Development1, to discuss the latest discoveries onthe developmental and evolutionary biology of these surpris-ingly complex “simple” animals. What follows is a brief ac-count of some of the highlights.

Many of the talks dealt directly, or indirectly, with eithercnidarian signalling pathways or transcription factors. Todate, representatives of virtually all the molecular systemsassociated with complex developmental change in bilateri-ans have been identified in cnidarians, many of which areactivated during regeneration of either the head or foot.(Hydra, in keeping with its mythological namesake, is capa-ble of growing a new head after amputation – or a new footafter a cut through the peduncle.) Fabian Rentzsch (Uni-versity of Darmstadt), for instance, described the early ap-pearance of Wnt activity at the tip of newly-forming heads.

All the major components of the standard Wnt signallingpathway, including b-catenin and TCF/LEF are found inHydra and appear to take part in the first events of headregeneration. Brigitte Galliot (University of Geneva) de-scribed other immediate early events in head regeneration,including the involvement of the CREB signalling pathwayand the early expression of several transcription factors.

One, perhaps unexpected, transcription factor encoded inthe Hydra genome is a putative orthologue of the T-box geneBrachyury (T). In triploblastic animals, T is associated withmesodermal development. As Ulrich Technau (Darmstadt)has shown, however, HyBra1 is expressed in the tip endodermof newly-developing heads. A second gene, Hybra2, which isless similar in sequence to the T gene of higher animals, isexpressed in the ectoderm. The results indicate that what weconsider to be “the” biological function of the T gene – namelyearly mesodermal specification – may, in reality, be a second-ary, co-opted function. Even within the hydrozoans, however,apparently orthologous T-box genes show differences in sitesand times of expression, as indicated by the work of MichaelKroiher (Cologne).

Another transcription factor expressed early in head re-generation is a member of the prd-like gene family, prdl-a.Other genes of this family, including members of the Paxgene subfamily are also present in cnidarians, including themore basal group, the anthozoa (the corals), as reported byDavid Miller (James Cook University, Australia). This indi-cates that much of the basic molecular evolution of this genefamily occurred well before bilaterian animals originated.

Another major gene family that is found in the cnidaria isthe Hox genes. Two Hox genes may be involved in differentways in regeneration. Cnox-3, a labial homologue, is ex-pressed in mature heads and regenerating head tissue.Cnox-2, a Deformed homologue, is expressed in the bodycolumn and may repress head formation. These expressionpattern of are reminiscent of the expression of their Dro-sophila counterparts along the A-P body axis of the fruit flybut this apparent homology between axes may yet prove tobe invalid. Christian Beetz (Tuebingen) presented severalarguments, including data on gene expression and musclepatterns, that the head-foot axis of Hydra is equivalent to,and perhaps the evolutionary precursor of, the dorso-ventral(neural-haemal) axis of higher animals.

Similarities between hydroids at the molecular and bio-chemical levels extend beyond transcription factors and sig-nalling to involve cell-cell matrix interactions and the moleculesthat mediate them. Michael Sarras (University of Kansas)described the evidence for extracellular matrix componentssuch as laminins, fibronectins, fibrillar collagen and collagen IV,and the essential roles of hydra matrix metalloproteinase inremodelling of the matrix in both tissue maintenance and footregeneration. In composition and behavior, cell-cell matrix in-teractions display a degree of complexity not expected in these

1The organizers were Profs. Thomas Bosch (University ofJena) and Charles David (University of Munich).

Adam S. Wilkins is at the BioEssays Editorial Office,10/11 Tredgold Lane, Napier Street, Cambridge CB1 1HN, UK.

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animals. Complexity is also a feature of the neural system.Hiroshi Shimizu (National Institute of Genetics, Mishima) de-scribed some elegant experiments that refute the notion of theHydra nervous system as a “diffuse” nerve net, incapable ofspecifying directional responses.

Hydra and other cnidarians also have a primitive immunesystem. Many years ago, Thomas Bosch and Charles David,building on earlier work by Richard Campbell, demonstratedthat Hydra has histo-incompatibility reactions in grafts be-tween strains. This early work implicated phagocytosis as ameans of eliminating the attacked cells but it is now appar-ent that apoptosis plays an important part, as well. SergeiKuznetsov (Jena) is characterizing the apoptotic eventsand searching for the first genes to be up-regulated. Inaddition, he has preliminary evidence that IgG related genesand a rel-system, similar to that of insects and mammals, isinvolved in the response of cnidarian cells to microbial in-fection. In Hydractinia, Luis Cadavid (Yale) described workthat provides the first mapping of an allorecognition locus incnidarians; the genes in the region are now being isolatedand characterized. Angelika Boettiger (Munich) de-scribed caspase genes and caspase enzyme activity asso-ciated with with apoptosis in Hydra. Since yeast cells lackcaspases and and do not undergo apoptosis, this funda-mental cellular process may have originated in early meta-zoans, perhaps in cnidaria.

Part of the complexity of cnidarians involves, of course,distinctive aspects of their biology. One of these is theproduction of a large number of signalling peptides.Toshitaka Fujisawa (Mishima) described the work ofthe Hydra peptide consortium, which involves laborato-

ries in Germany, Japan and the United States. Over 550peptides produced by Hydra have been identified, most ofwhich are produced as distinct entities rather than asdegradation products. About half of the 20-30 character-ized to date are neuropeptides, while others are involvedspecifically in signalling during regeneration activities. Inparticular, Thomas Bosch (Jena) described one, Heady,which is distinct from the classic Head Activator peptide,described many years ago by H.C. Schaller but which isalso involved in and required for head activation. Therequirement was demonstrated by the use of sequence-specific inhibitory, double-stranded RNA (RNAi) tech-nique. This technique has also been used effectively inother labs, for other genes, and promises to give animportant genetic dimension to cnidarian research, which,until recently, has been lacking.

Several other talks dealt with regeneration phenomenain cellular terms, dissecting out its components. The key-note address was delivered by Alfred Gierer (Tubingen).He began by reviewing the early history of work on Hydra,and some of the first experiments in zoology ever per-formed, by Abraham Tremblay, in the 18th century. Giererthen explained the development of his and Hans Mein-hardt’s ideas on reaction-diffusion mechanisms in pat-terning and how they may be extended to explain mor-phogenetic changes in animal development. ThoughHydra may seem a modest presence in the world of animalbiology today, it clearly has a distinguished history and,with its newly-appreciated status as the sister group forbilaterial metazoans, has much to offer in both develop-mental and evolutionary studies.

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