Finnerty Lab: Research Program

Research Program

Overview—Interdisciplinary research into the causes and consequences of Biodiversity.

Our main model system, the starlet sea anemone, Nematostella vectensis.

Position of Nematostella in metazoan phylogeny.

Ease of field-based & organismal research on Nematostella.

Developmental, cellular, molecular and genomic research on Nematostella.

Early findings from the Nematostella genome.

The origins of the Bilaterian body plan.

What is the selective advantage of Bilateral symmetry for a sessile cnidarian?

Developmental and reproductive flexibility of cnidarians.

Genetic evidence of sexual and asexual reproduction in natural populations.

The evolution of parasitism in Nematostella's sister genus.

In this era of rapid global change, one of the most urgent scientific challenges that we face is to understand the causes and consequences of biodiversity. This is a particularly complex problem for two reasons. First, both the causes and consequences of biodiversity span the entire biological hierarchy, from genome, to organism, to environment. Second, biodiversity is profoundly impacted by historical contingency.

If biologists are to achieve a genuine understanding of biodiversity, we must collectively achieve two goals. We must integrate data across levels of the biological hierarchy, and we must perform phylogenetic comparisons at multiple levels of evolutionary divergence (to place the origins of biological novelties in their appropriate historical contexts).

Watch an animation depicting the connection between genome, organism, and environment in the generation of biodiversity.

The Finnerty lab employs a highly interdisciplinary approach to study the causes of biodiversity and the origin of key evolutionary innovations. We are simultaneously investigating genomic innovations (e.g., Hox genes, stress-response pathways), organismal innovations (e.g., bilateral symmetry, developmental plasticity), and ecological innovations (e.g., shifts in ecological niche—from marine to estuarine, and from free-living to parasitic). Our interdisciplinary approach is made possible and rendered cohesive by our focus on a single model system that exhibits an unusual degree of experimental versatility—Nematostella vectensis.

Nematostella is an estuarine sea anemone that is native to the Atlantic coast of North America. In the early 1990’s, its potential value as a model system for developmental biology was first explicitly recognized. Over the last 10 years, its utility has extended far beyond developmental biology, due to its informative phylogenetic position, and its amenability to field studies, organismal studies, developmental studies, cellular studies, molecular and biochemical studies, and genomic studies

[Adult Nematostella polyp (left), egg mass (center), and "two-headed" adult undergoing fission by polarity reversal (left). Photo by Adam Reitzel]

i. Phylogenetic relationships. Nematostella is a member of the Cnidaria, one of the oldest metazoan phyla. The Cnidaria is a closely related outgroup to the Bilateria, the evolutionary lineage that comprises >99% of all extant animals. Comparisons between Nematostella and bilaterian model systems have helped to reconstruct the evolution of key animal innovations, including bilateral symmetry, mesoderm, and the nervous system.

ii. Field Studies. Nematostella’s environment (tidal creeks and salt marsh pools) is easily accessible from shore, and we have conducted extensive field surveys and collections throughout the species’ expansive range. Given the ecological importance of coastal estuaries, Nematostella is destined to become an important environmental sentinel species. (Photo of Sippewisset Marsh, Cape Cod; photo by JC Sullivan)

iii. Organismal Laboratory Studies. Nematostella is small, hardy, and gregarious, ideal for lab-based studies of ecology, behavior, and physiology. It can be cultured at high densities in finger bowls of standing artificial sea water. Its ability to regenerate facilitates the production of living genetic stocks.

iv. Development. Unlike the major developmental model systems (e.g., fruitfly, nematode, zebrafish, mouse, etc.) Nematostella has a complex developmental repertoire amenable to lab analysis. Adults can arise via (i) sexual reproduction, (ii) two forms of fission, or (iii) regeneration.

v. Cell Biology. Nematostella is amenable to cell culture techniques that have been developed for corals, thus facilitating studies on cellular physiology and differentiation.

vi. Molecular and Biochemical Studies. Unlike many marine invertebrates, it is easy to isolate “clean” DNA, RNA, or protein preparations. In situ hybridization produces results of spectacular clarity, so the spatiotemporal expression of genes can be monitored with unusual precision. An in situ experiment on Nematostella appears in the 7th edition of Developmental Biology, by Scott Gilbert (below).

vii. Genomic analyses. In less than ten years since the publication of the first molecular study on Nematostella, the starlet sea anemone became the first “basal” animal whose entire genome was sequenced.

Early Findings from the Nematostella Genome—Genomic sequences and large-scale EST projects are revealing that cnidarian genomes are surprisingly complex, and that they evolved in a relatively conservative fashion compared to the fruitfly or the soil nematode. Nematostella has already proven valuable for reconstructing the early evolution of animal genomes, and it will provide insights into the functional evolution of proteins implicated in human disease. Four recent studies from my lab are mentioned here.

1) Homeobox genes. We uncovered a surprisingly rich complement of homeobox genes in Nematostella, identifying the first known cnidarian representatives of the TALE, HNF, and CUT homeodomain classes and eighteen distinct Hox-related genes, many of which reside in genomic clusters. Nematostella possesses substantially more homeodomains than the fruitfly (130 versus 98). [Obtain article]

2) The NF-kappaB signaling pathway. is an intensively studied signaling protein that plays a critical role in mediating organismal stress responses and immune function in vertebrates and insects. We identified this protein in Nematostella, along with numerous additional members of the y—the first time that NF-kB has been reported in a “basal” animal. [View abstract]

3) Ancient Intron Conservation. Sixty-nine percent (862/1246) of human introns in 343 orthologous genes are conserved in Nematostella, which greatly exceeds the conservation between humans and fruitfly (14%), mosquito (13%) or nematode (19%). Thus, many human introns originated before the cnidarian-bilaterian split, and many introns have been shifted or lost during the evolution of fruitfly, mosquito, and nematode.
(Phylogeny reproduced from Sullivan, Reitzel, and Finnerty, Genome Informatics (2006) groups taxa based upon their shared possession of introns. Human groups with sea anemone to the exclusion of the more closely related fruitfly, mosquito, and soil nematode. [Obtain article])

4) Homologs of Human Disease Genes. Nematostella harbors slightly more clear orthologs of human disease genes than fruitfly or nematode, and in some cases where these three genomic models possess a homolog of a human disease gene, the anemone gene is most similar to the human gene.

The Origins of the Bilaterian Bodyplan. Bilateral symmetry is widely considered to be a key innovation of the Bilateria, partially responsible for the remarkable evolutionary success of this lineage. Most invertebrate zoology textbooks (and some articles in the recent scientific literature) continue to emphasize that cnidarians are essentially radial. However, many corals and sea anemones exhibit true bilateral symmetry, and our research suggests that this fundamental body plan feature could be homologous in Cnidaria and Bilateria. If bilateral symmetry was present in the cnidarian-bilaterian ancestor, then both lineages inherited homologous developmental mechanisms for patterning their primary and secondary body axes. In bilaterian animals, Hox and ParaHox genes play a conserved role in patterning the primary (anterior-posterior) axis, and Dpp plays a conserved role in patterning the secondary (dorsal-ventral) axis. Our work has helped to demonstrate that these key regulators of animal development originated prior to the split between the Cnidaria and the Bilateria. In 1999, we demonstrated the presence of both Hox and ParaHox genes in Cnidaria (view abstract), and in 2004, we reported on the recovery of a Dpp homolog in Nematostella (view abstract).

In 2003, we showed that the ParaHox gene Gsx is expressed only in the oral region of Nematostella, the kind of axial restriction you would expect if this gene is involved in patterning the main body axis (view abstract). In 2004, we described the expression of five Hox genes and Dpp in Nematostella, providing molecular support for the homology of bilateral symmetry in Cnidaria and Bilateria (view abstract). The five Hox genes we described are expressed in three distinct axial domains—the pharynx, the body column, and the foot. Collectively, these domains account for nearly the entire primary body axis. This pattern of Hox expression along the oral-aboral axis of Nematostella is reminiscent of the “Hox code” that patterns the anterior-posterior axis of Bilateria. Dpp is expressed asymmetrically about the blastopore during the gastrula stage, consistent with an earlier study performed on the coral Acropora. However, we observed a novel and more interesting aspect of Dpp expression much later in development. In the late larval stage, Dpp is expressed asymmetrically along the directive axis. The directive axis is the animal’s secondary axis of polarity, comparable to the dorsal-ventral axis of Bilateria. Our more recent phylogenetic, genomic, and developmental analysis of 18 Hox and Hox-related genes in Nematostella bolsters these conclusions (obtain article).

Why Has Selection Favored the Evolution of Bilateral Symmetry in Cnidarians? should exhibit bilateral symmetry. The textbook explanation for the origin of bilateral symmetry is that it evolved under selection to improve the efficiency of directed locomotion. Indeed, most animals that exhibit bilateral symmetry engage in directed swimming or crawling with the body held in a consistent orientation relative to the direction of locomotion (e.g., dorsal directed up, and anterior directed forward). However, this hypothesis cannot explain the widespread occurrence of bilateral symmetry in the Cnidaria because cnidarians do not engage in directed locomotion where the body is held in a consistent orientation relative to the direction of travel. Recently, I suggested a viable alternative: that bilateral symmetry could have evolved under selection to improve internal fluid-flow in a sessile animal (Finnerty 2005, view abstract). If bilateral symmetry is homologous in cnidarians and bilaterians, this might explain the origin of bilateral symmetry in the Bilateria itself.

Developmental and Reproductive Flexibility. Relative to the major animal models in developmental biology (e.g., vertebrates, fruitflies, and nematodes), cnidarians exhibit a stunning degree of developmental and reproductive flexibility. An adult cnidarian may be formed via three distinct developmental pathways: (1) embryogenesis following sexual reproduction; (2) asexual reproduction by fission or budding; (3) regeneration following injury. In fact, Nematostella is capable of two distinct forms of asexual fission that we have termed “physal pinching” and “polarity reversal.” (Darling et al., 2005, view abstract) In physal pinching, the terminal foot (or physa) is pinched off, and the small asexual propagule then regenerates a new body column and head. Throughout this process, the developing propagule maintains the original axial orientation that it inherited from the “parent” animal. By contrast, during polarity reversal, a new head forms at the site of the existing foot. A complete axis duplication then occurs, resulting in a “two-headed monster,” where two individuals exhibiting the opposite polarity are attached at the foot. Fission then separates two large and fully functioning individuals. These two-headed monsters was originally regarded as developmental anomalies—e.g., failed regeneration—but we have shown that this process occurs spontaneously (without injury) and documented it Edwardsiella lineata, a related species.

The Development, Ecology and Evolution of Reproductive Flexibility. The reproductive and developmental flexibility of Nematostella (and other Cnidaria) raises a number of profound evolutionary questions. How is this flexibility encoded in the genomes and developmental programs of these animals, and why is it lacking in most other animals? How do the animals “decide” whether to reproduce via sexual or asexual means? How does such reproductive flexibility affect the course of evolution? We are attacking this problem at multiple levels (molecular, organismal, and ecological). At the molecular level, we are currently comparing the expression of developmental genes across all three pathways using in situ hybridization. We are studying the effects of various environmental treatments on the sexual and asexual reproduction of laboratory populations of Nematostella. We have surveyed dozens of wild Nematostella populations using the AFLP genetic fingerprinting technique. (e.g., Darling et al. 2004, view abstract). AFLPs reveal substantial variation in the degree to which sexual or asexual reproduction drive population increases in natural populations. We have also collected hundreds of Nematostella from dozens of wild populations along the coast of New England, the Mid-Atlantic, and the Southeast, and we are making these living genetic stocks available as a resource to the scientific and educational communities at Nematostella.org.

Ecology and Evolution of Parasitism in the Lined Sea Anemone, Edwardsiella lineata. Developmental comparisons between Cnidaria and Bilateria are limited by the antiquity of their divergence (>600 million years ago) and the drastic differences between their body plans — e.g., no body part on a fruit fly is homologous to any body part on a sea anemone. Comparisons among more closely related species can yield more detailed information on the evolution of developmental mechanisms and anatomical structures, but closely related species typically don’t differ with respect to major bodyplan features. We are using ecological studies, gene expression assays, gene sequence comparisons, and genomic approaches to understand the evolution of cnidarian developmental diversity by comparing Nematostella to the closely related Edwardsiid sea anemone Edwardsiella lineata. Edwardsiella has evolved a novel facultative, parasitic life history that involves a new parasitic life-history stage with a unique body plan (Reitzel et al., 2006, view abstract). In the photo below, several worm-like parasitic anemones can be seen surrounding the stomach of the ctenophore Mnemiopsis (lower left). The mouth of the ctenophore, surrounded by its large oral lobes, is to the upper right.