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Development of the motor nervous system in ascidians.

The motor nervous system of adult ascidians consists of neurons forming the cerebral ganglion from which axons run out directly to the effectors, i.e., muscular and ciliary cells. In this study, we analyzed the development of the motor fibers, correlating this with organ differentiation during asexual reproduction in Botryllus schlosseri. We used a staining method for acetylcholinesterase, whose reaction product is visible with both light and electron microscopy and which labels entire nerves, including their thin terminals, making them identifiable between tissues. While the cerebral ganglion is forming, the axons elongate and follow stereotypical pathways to reach the smooth muscle cells of the body, the striated muscle of the heart, and the ciliated cells of the branchial stigmata and the gut. A strict temporal relation links the development of the local neural network with its target organ, which is approached by nerves before the effector cells are fully differentiated. This process occurs for oral and cloacal siphons, branchial basket, gut, and heart. Axons grow through the extracellular matrix and arrive at their targets from different directions. In some cases, the blood sinuses constitute the favorite roads for growing axons, which seem to be guided by a mechanism involving contact guidance or stereotropism. The pattern of innervation undergoes dynamic rearrangements and a marked process of elimination of axons, when the last stages of blastogenesis occur. The final pattern of motor innervation seems to be regulated by axon withdrawal, rather than apoptosis of motor neurons.

Animals↗

Novel, secondary sensory cell organ in ascidians: in search of the ancestor of the vertebrate lateral line.

A new mechanoreceptor organ, the "coronal organ," located in the oral siphon, is described by light and electron microscopy in the colonial ascidians Botryllus schlosseri and Botrylloides violaceus. It is composed of a line of sensory cells (hair cells), accompanied by supporting cells, that runs continuously along the margin of the velum and tentacles of the siphon. These hair cells resemble those of the vertebrate lateral line or, in general, the acoustico-lateralis system, because they bear a single cilium, located centrally or eccentrically to a hair bundle of numerous stereovilli. In contrast to other sensory cells of ascidians, the coronal hair cells are secondary sensory cells, since they lack axonal processes directed towards the cerebral ganglion. Moreover, at their base they form synapses with nerve fibers, most of which exhibit acetylcholinesterase activity. The absence of axonal extensions was confirmed by experiments with lipophilic dyes. Different kinds of synapses were recognized: usually, each hair cell forms a few afferent synapses with dendrites of neurons located in the ganglion; efferent synapses, both axo-somatic (between an axon coming from the ganglion and the hair cell) and axo-dendritic (between an axon coming from the ganglion and an afferent fiber) were occasionally found. The presence of secondary sensory cells in ascidians is discussed in relation to the evolution of sensory cells and placodes in vertebrates. It is proposed that the coronal organ in urochordates is homologous to the vertebrate acoustico-lateralis system.

Acetylcholine↗

Cell reorganisation during epithelial fusion and perforation: the case of ascidian branchial fissures.

In this study, we have analysed ultrastructurally the mechanism of epithelial fusion and perforation during the development of branchial fissures in the larva and bud of the colonial urochordate Botryllus schlosseri. Perforation of membranes represents an important process during embryogenesis, occurring to create communication between two separate compartments. For example, all chordate embryos share the formation of pharyngeal plates, which are constituted of apposed endodermal and ectodermal epithelia, which have the capacity to fuse and perforate. Although the process of perforation is extremely common, its cellular mechanism remains little understood in detail, because of the complexity of the structures involved. In B. schlosseri, two epithelial monolayers, the peribranchial and the branchial ones, with no interposed mesenchymal cells, participate in pharyngeal perforation. Blood flows in the interspace between the two cellular leaflets. Apico-lateral zonulae occludentes seal the cells of each epithelium, so that the blood compartment is separated from the environment of the peribranchial and branchial chambers; here, sea water will flow when the zooid siphons open. Stigmata primordia appear as contiguous thickened discs of palisading cells of branchial and peribranchial epithelia. The peribranchial component invaginates to contact the branchial one. Here, the basal laminae intermingle, compact, and are degraded, while the intercellular space between the two epithelia is reduced to achieve the same width as that found between the lateral membranes of adjacent cells. Cells involved in this fusion rapidly change their polarity: they acquire a new epithelial axis, because part of the adhering basal membrane becomes a new lateral surface, whereas the original lateral membranes become new apical surfaces. Before disassembling the old tight junctions and establishing communication between branchial and peribranchial chambers, cells of the stigmata rudiments form new tight junctions organised as distinct entities, so that the structural continuum of the epithelial layers is maintained throughout the time of fusion and perforation.

Animals↗

Divergent roles of the DEAD-box protein BS-PL10, the urochordate homologue of human DDX3 and DDX3Y proteins, in colony astogeny and ontogeny.

Proteins of the highly conserved PL-10 (Ded1P) subfamily of DEAD-box family, participate in a wide variety of biological functions. However, the entire spectrum of their functions in both vertebrates and invertebrates is still unknown. Here, we isolated the Botryllus schlosseri (Urochordata) homologue, BS-PL10, revealing its distributions and functions in ontogeny and colony astogeny. In botryllid ascidians, the colony grows by increasing the number of modular units (each called a zooid) through a whole colony synchronized and weekly cyclical astogenic budding process (blastogenesis). At the level of the colony, both BS-PL10 mRNA and its protein (78 kDa) fluctuate in a weekly pattern that corresponds with the animal's blastogenic cycle, increasing from blastogenic stage A to blastogenic stage D. At the organ/module level, a sharp decline is revealed. Primary and secondary developing buds express high levels of BS-PL10 mRNA and protein at all blastogeneic stages. These levels are reduced four to nine times in the new set of functional zooids. This portrait of colony astogeny differed from its ontogeny. Oocytes and sperm cells express high levels of BS-PL10 protein only at early stages of development. Young embryos reveal background levels with increased expressions in some organs at more developed stages. Results reveal that higher levels of BS-PL10 mRNA and protein are characteristic to multipotent soma and germ cells, but patterns deviate between two populations of differentiating stem cells, the stem cells involved in weekly blastogenesis and stem cells involved in embryogenesis. Two types of experimental manipulations, zooidectomy and siRNA assays, have confirmed the importance of BS-PL10 for cell differentiation and organogenesis. BS-PL10 (phylogenetically matching the animal's position in the evolutionary tree), is the only member of this subfamily in B. schlosseri, featuring a wide range of biological activities, some of which represent pivotal roles. The surprising weekly cyclical expression and the participation in cell differentiation posit this molecule as a model system for studying PL10 protein subfamily.

Amino Acid Sequence↗

Failure to find alloimmune memory in the resorption phenomenon of Botryllus cytomictical chimera.

It has been previously shown that mixed-cell chimeras may be established between different colonies of the compound tunicate Botryllus schlosseri given that they share one allele in common on the fusibility locus. However, one of the partners in each chimera is often resorbed. Here we tested for the existence of a memory component to this response, as measured by the accelerated interval to resorption of a second set of semiallogeneic colonies. Eight genetically unrelated colonies gave rise to eighteen chimeras. After a complete resorption of the "inferior" partners in these chimeras, secondary and tertiary sets of chimeras were established with some of them by fusion of the "superior" with naive subclones of the "inferior" partners. It is shown here that (a) when multiple chimeras are prepared using the same pair of colonies, subclones of only one of the partners are resorbed; (b) high variation in the time for resorption is recorded when several chimeras are prepared from any specific pair of colonies, and (c) the time for resorption is not related to the number of vessels connecting between the partners in the chimera, nor to their relative body sizes. Allospecific memory is not documented here and reasons for its absence are discussed.

Animals↗

Neurogenic and non-neurogenic placodes in ascidians.

The late differentiation of the ectodermal layer is analysed in the ascidians Ciona intestinalis and Botryllus schlosseri, by means of light and electron microscopy, in order to verify the possible presence of placodal structures. Cranial placodes, ectodermal regions giving rise to nonepidermal cell types, are classically found exclusively in vertebrates; however, data are accumulating to demonstrate that the nonvertebrate chordates possess both the genetic machinery involved in placode differentiation, and ectodermal structures that are possible homologues of vertebrate placodes. Here, the term "placode" is used in a broad sense and defines thickenings of the ectodermal layer that can exhibit an interruption of the basal lamina where cells delaminate, and so are able to acquire a nonepidermal fate. A number of neurogenic placodes, ones capable of producing neurons, have been recognised; their derivatives have been analysed and their possible homologies with vertebrate placodes are discussed. In particular, the stomodeal placode may be considered a multiple placode, being composed of different sorts of placodes: part of it, which differentiates hair cells, is discussed as homologous to the octavo-lateralis placodes, while the remaining portion, giving rise to the ciliated duct of the neural gland, is considered homologous to the adenohypophyseal placode. The neurohypophyseal placode may include the homologues of the hypothalamus and vertebrate olfactory placode; the rostral placode, producing the sensorial papillae, may possibly be homologous to the placodes of the adhesive gland of vertebrates.

Animals↗

Ascidian neural crest-like cells: phylogenetic distribution, relationship to larval complexity, and pigment cell fate.

Migratory neural crest-like cells, which express the cell surface antigen HNK-1 and develop into pigment cells, have recently been identified in the ascidian Ecteinascidia turbinata. Here we use HNK-1 expression as a marker to determine whether neural crest-like cells are responsible for pigment development in diverse ascidian species. We surveyed HNK-1 expression and tyrosinase activity in 12 ascidian species, including those with different adult organizations, developmental modes, and larval sizes and complexities. We observed HNK-1 positive cells in every species, although the timing of HNK-1 expression varied according to the extent of larval complexity. HNK-1 expression was initiated during the late tailbud stage in species in which adult features are formed precociously in large complex larvae. In contrast, HNK-1 positive cells did not appear until the swimming tadpole or juvenile stage in species with small simple larvae in which most adult features appear after metamorphosis. Double labeling experiments indicated that HNK-1 and tyrosinase are expressed in the same subset of pigment-forming mesenchymal cells in species with complex or simple larvae. In addition, the absence of HNK-1 and tyrosinase expression in albino morphs of the colonial ascidian Botryllus schlosseri suggested that the major fate of neural crest-like cells is to become pigment cells. The results suggest that ascidian neural crest-like cells and vertebrate neural crest cells had a common origin during chordate evolution and that their primitive function was to generate body pigmentation.

Animals↗

Comparative studies on the structure of reproductive organs of four botryllid ascidians.

Reproductive organs of four botryllid ascidians, Botryllus primigenus, Botryllus schlosseri, Botrylloides violaceus and Botrylloides leachi, were studied histologically. In every species, the egg follicle consisting of an egg and its inner and outer follicles, is attached to the follicle stalk, the vesicle being composed of a flat epithelium, which in its turn is connected to the atrial epithelium or to the brood pouch specialized from it. In B. schlosseri, the egg is ovulated into the atrial cavity and remains there held by the brood cup, of which the inner epithelium is derived from the follicle stalk and the outer one from the atrial epithelium. In B. primigenus, the brood pouch develops as a diverticulum of the atrial cavity, around the entrance of which a fold differentiates from the atrial epithelium and closes the pouch during embryogenesis. In both species of Botrylloides, the brood pouch is formed by the outgrowth of the thickened atrial epithelium into the blood space, the entrance of which is closed during embryogenesis. The discarded outer follicle completely disintegrates soon after ovulation in B. schlosseri, but part of it remains throughout embryogenesis in the blood space in B. primigenus or projecting into the interior of the brood pouch in Botrylloides. In primigenus, the testis, when it accompanies the egg follicle, is placed at the bottom of the brood pouch and the sperm is shed through the pouch prior to ovulation. In B. schlosseri and the Botrylloides species, the testis is located independently from the egg follicle and the sperm matures after ovulation.

Animals↗

Cyclical generation and degeneration of organs in a colonial urochordate involves crosstalk between old and new: a model for development and regeneration.

Botryllus schlosseri is a colonial marine urochordate in which all adult organisms (called zooids) in a colony die synchronously by apoptosis (programmed cell death) in cyclical fashion. During this death phase called takeover, cell corpses within the dying organism are engulfed by circulating phagocytic cells. The "old" zooids and their organs are resorbed within 24-36 h (programmed cell removal). This process coincides temporally with the growth of asexually derived primary buds, that harbor a small number of undifferentiated cells, into mature zooids containing functional organs and tissues with the same body plan as adult zooids from which they budded. Within these colonies, all zooids share a ramifying network of extracorporeal blood vessels embedded in a gelatinous tunic. The underlying mechanisms regulating programmed cell death and programmed cell removal in this organism are unknown. In this study, we extirpated buds or zooids from B. schlosseri colonies in order to investigate the interplay that exists between buds, zooids, and the vascular system during takeover. Our findings indicate that, in the complete absence of buds (budectomy), organs from adult zooids underwent programmed cell death but were markedly impaired in their ability to be resorbed despite engulfment of zooid-derived cell corpses by phagocytes. However, when buds were removed from only half of the flower-shaped systems of zooids in a colony (hemibudectomy), the budectomized zooids were completely resorbed within 36-48 h following onset of programmed cell death. Furthermore, if hemibudectomies were carried out by using small colonies, leaving only a single functional bud, zooids from the old generation were also resorbed, albeit delayed to 48-60 h following onset of programmed cell death. This bud eventually reached functional maturity, but grew significantly larger in size than any control zooid, and exhibited hyperplasia. This finding strongly suggested that components of the dying zooid viscera could be reutilized by the developing buds, possibly as part of a colony-wide recycling mechanism. In order to test this hypothesis, zooids were surgically removed (zooidectomy) at the onset of takeover, and bud growth was quantitatively determined. In these zooidectomized colonies, bud growth was severely curtailed. In most solitary, long-lived animals, organs and tissues are maintained by processes of continual death and removal of aging cells counterbalanced by regeneration with stem and progenitor cells. In the colonial tunicate B. schlosseri, the same kinds of processes ensure the longevity of the colony (an animal) by cycles of death and regeneration of its constituent zooids (also animals).

Animals↗

Cytoskeleton alterations by tributyltin (TBT) in tunicate phagocytes.

The effects of tributyltin chloride (TBT) on cytoskeletal components, as possible cell targets of toxicity, were examined on cultured hemocytes of the colonial ascidian Botryllus schlosseri by means of indirect immunofluorescence. The immunotoxic effect of 10 microM TBT (sublethal concentration) consists of (1) inhibition of yeast phagocytosis, Ca2+ ATPase activity, and respiratory burst; (2) increase in intracellular Ca2+ concentration; and (3) alterations in cell morphology. After 60 min, TBT-exposed amebocytes become spherical, withdrawing their long pseudopodia, and lose motility. Their microfilaments assemble in clusters around the peripheric cytoplasm, indicating massive disassembly, with the exception of unaltered adhesion plaques. Analogously, their microtubules reveal extensive disaggregation, being scattered in the cytoplasm and not recognizable as single filaments, whereas the microtubule organizing center (MTOC) is still visible. Treatment together with 20 micrograms/ml calmodulin (CaM) can partially restore the cytoskeleton architecture. These results suggest a relationship between TBT and Ca2+ homeostasis in ascidian hemocytes. By interfering with Ca2+ ATPase activity through CaM inhibition, either directly or indirectly, TBT induces an excess of intracellular Ca2+ accumulation, which first causes internal disorganization of cytoskeletal proteins and consequently inhibition of phagocytosis, beginning from chemotaxis and particle adhesion.

Animals↗

Initial characterization of a protochordate histocompatibility locus.

The colonial protochordate, Botryllus schlosseri, undergoes a natural transplantation reaction which is controlled by a single, highly polymorphic locus called the Fu/HC. We are using map-based cloning to identify Fu/HC gene(s), and have currently delineated their location to an approximately 1-cM region of the B. schlosseri genome. The Fu/HC physical map currently consists of 85 sequence-tagged sites mapped on a minimum tiling path of 800 kb which consists of five contigs, with four gaps remaining to be crossed, and is estimated to be 75% completed. Approximately half this region has been sequenced throughout the locus, allowing the first analysis of a metazoan histocompatibility locus outside of vertebrates. This has resulted in the identification of 18 predicted genes, a number of which have been found to be expressed. Several of these genes are well conserved among the chordates; however, none of the predicted or expressed genes are linked within the genome of any organism in the databases. In addition, the Fu/HC is one of the most polymorphic loci ever described, and physical mapping has revealed that the locus is quite dynamic, and includes features such as hotspots of recombination.

Animals↗

Marine invertebrate cell cultures: new millennium trends.

This review analyzes activities in the field of marine invertebrate cell culture during the years 1999 to 2004 and compares the outcomes with those of the preceding decade (1988 to 1998). During the last 5 years, 90 reports of primary cell culture studies of marine organisms belonging to only 6 taxa (Porifera, Cnidaria, Crustacea, Mollusca, Echinodermata, and Urochordata) have been published. This figure represents a 2-fold increase in the annual number of publications over the decade 1988 to 1998. Three other trends distinguish the two reviewed periods. First, in recent years studies attempting to improve cell culture methodologies have decreased, while interest in applications of already existing methodologies has increased. This reflects the effects of short-term cultures in attracting new researchers and scientific disciplines to the field. Second, only 17.8% of the recent publications used long-term cultures, compared with 30.0% of the publications in the previous decade. Third, during recent years research in cell cultures has studied fewer model species more extensively (mainly, Botryllus schlosseri, Crassostrea, Mytilus, Penaeus, and Suberites domuncula), signifying a shift from previous investigations that had studied a more diverse range of organisms. From 1988 to 1998 the phylum Mollusca was the most studied taxon (34.4%), but recent years have seen more studies of Porifera and Crustacea (30.0% and 32.2% of publications) than of Mollusca (21.1%). Still, not even a single established cell line from any marine invertebrate has yet been made available. However, the use of new cellular, genomic, and proteomic tools may fundamentally change our strategy for the development of cell cultures from marine invertebrates.

Animals↗

Allogeneic resorption in colonial protochordates: consequences of nonself recognition.

Colonial tunicates (protochordates of the subfamily Botryllinae) have the property of forming natural chimeras in the wild or in the laboratory with other members of the same species if both individuals share at least one allele at a single highly polymorphic locus, termed the fusibility/histocompatibility (Fu/HC) locus. Laboratory studies revealed that after the establishment of a common blood circulatory system between a fusible pair one of the colonies in the chimera is usually resorbed, a phenomenon that occurs after an interval of 1 week or extends to up to 8 months. In the present article, we review this allogeneic resorption in Botryllus schlosseri, a cosmopolitan protochordate. The studies on allogeneic resorption in B. schlosseri revealed 13 typical characteristics. However, several processes interrupt successful resorption, such as the retreat growth phenomenon, chimeric death, and others. It was also found that allogeneic resorption is not only genetically controlled but is also controlled by a polymorphic hierarchial phenomenon, including the Fu/HC locus and additional unrelated loci. One basic rule for this genetic system is that colonies heterozygotic on the resorption elements will resorb more homozygotic partners. This colony resorption, expressed by a morphological elimination of one partner, is probably manifested by cellular elements circulating in the tunicate blood system. However, it was also shown that some blood-borne cells of the inferior partner, such as the stem cells, may escape resorption, a phenomenon that raises the threat of germ/somatic cell parasitism.

Alleles↗

Characteristics of allogeneic resorption in Botrylloides from the Mediterranean coast of Israel.

Some of the characteristics of allogeneic resorption have been revealed in studies of chimeras of two Botrylloides subpopulations (SP1 and SP3) inhabiting the Mediterranean coast of Israel. Both Botrylloides SPs exhibited the same outcomes, which differ significantly from the resorption documented in the well-studied botryllid ascidian, Botryllus schlosseri: 1. Resorption in Botrylloides chimeras was usually a very fast process starting 1 to 26 days after fusion and terminating in < 9 days thereafter. 2. Resorption occurs at any blastogenic stage. 3. Resorption is complete, including zooids, buds, blood vessels and ampullae. 4. Either one of the genotypes can be resorbed in multipair chimeras of any specific combination. 5. Resorption starts simultaneously in all zooids of the partner to be resorbed. 6. Time for resorption and directionality were not affected by the size ratios between the partners (0.3-1.8). As in B. schlosseri, other phenomena (disconnection, chimeric death and retreat growth) interrupt resorption in ca. 60% of the chimeras, under laboratory conditions. We propose that external stress conditions also have a significant role in a nonimmunological expression of resorption in Botrylloides.

Animals↗

Cloning of a urochordate cDNA featuring mammalian short consensus repeats (SCR) of complement-control protein superfamily.

Mammalian tumor necrosis factor (TNF)-alpha degenerate polymerase chain reaction (PCR) primers were used to amplify a probe from Botryllus schlosseri (colonial ascidian) allogeneic rejection-cDNA library. A PCR product (269 bp) was cloned and sequenced encoding an open reading frame (ORF) of 89 amino acids (aa). This clone, which revealed no similarity to TNF-alpha, but a substantial similarity to mammalian proteins featuring short consensus repeats (SCRs) of the complement control superfamily, was used to probe the rejection-cDNA library. Two partial cDNA clones were isolated and sequenced (Bs.1, 846 bp; Bs.2, 712 bp). The longest ORF in clone Bs.1 (which lacks the 5' end of the cDNA) predicts a protein of 251 aa, which differs from Bs.2 at six nucleotides and four aa. We compare the aa similarity (up to 50.5%) of Bs.1 with the SCR-region of mammalian complement factor H, apolipoprotein H, selectins, and complement receptors type 1 and type 2. A somatomedin B-like domain at the C-terminus of Bs.1 deduced protein was also recorded. We propose that this mosaic and polymorphic botryllid sequence, featuring mammalian-like SCRs, might be an ancestral molecule in the evolution of the chordate's complement-control protein superfamily.

Amino Acid Sequence↗

External amebocytes guard the pharynx entry in a tunicate (Ascidiacea).

In the present report, we describe the identification of unusual free amebocytes, completely exposed to seawater, which inhabit the inner surface of the oral and atrial siphons of the compound ascidian Botryllus schlosseri (Urochordata). The origin and biological role of these cells were studied by cytochemical and ultrastructural analysis. These amebocytes are mononucleate cells, with numerous round granules, varying in content, and long filopodia, which contact the cuticle protrusions of the tunic in the siphon. Histochemical, histoenzymatic and immunohistochemical assays were carried out under light microscopy on sections and on living and fixed cultured hemocytes. Results showed that the phagocytic blood cells and the free amebocytes of the siphons shared: (i) affinity for the alpha-mannose specific agglutinin of Narcissus pseudonarcissus (NPA), (ii) occurrence of hydrolytic activities of acid phosphatase and non-specific esterases inside lysosomal vesicles and large vacuoles, (iii) membrane labeling with the lipophilic dye PKH26 specific for phagocytic cells, (iv) anti-CD39 immunocytochemical labeling specific for lysosomes of mammalian macrophages. All histochemical data support the hypothesis that these cells are 'sentinel cells' belonging to the hyaline amebocyte population of the phagocytic differentiation line of the immunocytes, since they can also recognize and phagocytize carmine experimentally administered as target particles.

Acid Phosphatase↗

Tributyltin-sulfhydryl interaction as a cause of immunotoxicity in phagocytes of tunicates.

We reported elsewhere that tributyltin (TBT) has detrimental effects on the immune system of the colonial ascidian Botryllus schlosseri, through interaction with calmodulin and alteration of Ca2+ homeostasis. Here, we studied the capability of TBT to react with intracellular thiols. After exposure to 0.1 microM TBT, a significant decrease in B. schlosseri hemocytes stained for total thiols and reduced glutathione (GSH) was detected. Exogenous sulfhydryl and sulfide compounds can prevent TBT-induced cell morphology alterations and decrease the percentage of tin-containing hemocytes, indicating the scavenging ability of thiol peptides. No effects were observed with disulfides, N-acetylcysteine, or the GSH fragment Cys-Gly. No interactions were observed with TBT and carmustine, whereas TBT and N-ethylmaleimide (NEM) showed a combined antagonistic action, suggesting direct interaction of TBT with thiol-containing compounds. Regulation of Ca2+ efflux from internal stores seems to depend on stimulation of the inositol 1,4,5-trisphosphate (InsP3) receptor by oxidized glutathione (GSSG), which results from interactions of both TBT-GSH and TBT-GSH reductase.

Animals↗

fester, A candidate allorecognition receptor from a primitive chordate.

Histocompatibility in the primitive chordate, Botryllus schlosseri, is controlled by a single, highly polymorphic locus, the FuHC. By taking a forward genetic approach, we have identified a locus encoded near the FuHC, called fester, which is polymorphic, polygenic, and inherited in distinct haplotypes. Somatic diversification occurs through extensive alternative splicing, with each individual expressing a unique repertoire of splice forms, both membrane bound and potentially secreted, all expressed in tissues intimately associated with histocompatibility. Functional studies, via both siRNA-mediated knockdown and direct blocking by monoclonal antibodies raised against fester, were able to disrupt predicted histocompatibility outcomes. The genetic and somatic diversity, coupled to the expression and functional data, suggests that fester is a receptor involved in histocompatibility.

Alleles↗