The Xenopus Anatomical Ontology
In the Xenopus Anatomical Ontology (XAO) we have described X. laevis anatomy as a controlled, structured vocabulary of the set of structures and tissues that exists throughout development. Items in the XAO, which we here call "types" as recommended by Smith et al. 12, exist in a graphical structure where they may have multiple "parents" or multiple "children" and are connected by relationships. A given tissue may be asserted to be part_of another tissue and it may be classified as a subtype of another tissue, with which it is said to have an "is_a" relationship. We have arranged the XAO's topmost nodes using CARO, the Common Anatomy Reference Ontology, as a template, and CARO's relationships and definitions 10 have been adopted for these structure types. As an essential framework for representing developmental events, we have incorporated the complete Nieuwkoop and Faber staging series into the ontology. The 66 stage types in this sub-ontology and their definitions (including time since fertilization and external staging criteria) have been compiled from the Normal Table of Xenopus development 1. Individual NF stages have been grouped into six superstages: cleavage, blastula, gastrula, neurula, tailbud and tadpole. The XAO represents the transformation, fission, and fusion of structures and tissues throughout embryonic and larval development with a network of develops_from relationships between them.
Each type in the ontology has been automatically assigned a unique identifier that has two components, an approved abbreviation for the ontology (XAO) and a serial number associated with only that entity. An ID remains stable even if the agreed-upon nomenclature for a structure or tissue changes. If a type is later designated as "obsolete", its ID will not be re-used for a new term. Synonyms, including plural forms, have also been assigned to several structures and tissues.
Stage types have been organized according to recommendations by the CARO working group 10. Their relative timing is indicated by preceded_by relationships (for instance, "NF stage 7" is preceded_by "NF stage 6.5"). The series of stages has given us a basis for indicating the time during which an anatomical structure or tissue is known to exist by creating start- and end-stage relationships, e.g. "pronephric kidney" starts_during "NF stage 29/30" and ends_during "NF stage 55". We have taken each anatomical type's other relationships into account when curating stage range information, adopting rules first developed for the Zebrafish Anatomical Ontology 13: types with is_a and part_of relationships follow the rule that a child must exist within the range of its parent and types with develops_from relationships follow the rule that a child's range must overlap or abut the range of its parent. Thus in the timeline of embryonic and larval development, for "pronephric kidney" to have a valid develops_from relationship to its parent "pronephric mesenchyme", it must be specified as appearing no later than stage 31 (late tailbud), the NF stage immediately following the latter's end stage; and "glomus", being part_of "pronephric kidney", must not be specified to exist outside of the stage 29/30 to 55 range.
We have written type definitions that adhere to the OBO Foundry's recommended "genus-differentia" format 6; e.g., "cell" (XAO: 0003012) is defined as an "anatomical structure" (the "genus") that has as its parts "a maximally connected cell compartment surrounded by a plasma membrane" (the "differentia", or distinguishing property or set of properties that sets off this entity from other anatomical structures), and "pigment cell" (XAO: 0003014) is a "cell (genus) that contains coloring matter (differentia)".
The XAO contains 87 stage types, including superstages, and 626 anatomical types. Xenopus development is represented by 308 develops_from relationships. "Embryo" (XAO:0000113) and "anatomical structure" (XAO:0003000) are high-level nodes of the anatomical ontology and provide the starting points for a developmental map and for a structural classification scheme, respectively. The map of Xenopus development is organized by primary germ layer. The sensorial layer of ectoderm provides an example of the lineage information that can be found (Figure 1); in the XAO several lineages have a depth of four or five nodes. In the "anatomical structure" classification scheme, many tissues have been organized under five "organism subdivisions": the head, trunk, tail, limbs and surface structures. In addition, tissues have been classified in eleven anatomical systems (e.g., the nervous system). The lateral line system, for example, is represented as a part of the nervous system, as a surface structure, and as a derivative of ectoderm, allowing it to be found either by structural subdivision or by lineage.
<p>Figure 1</p>
A portion of the Xenopus Anatomical Ontology's developmental map
A portion of the Xenopus Anatomical Ontology's developmental map. Shown are the anatomical features to which the sensorial layer of the ectoderm gives rise. Types in green boxes have develops_from relationships to their parents. Also shown here are examples of the other two anatomical relationships that are integral to the XAO: ectoderm is_a primary germ layer; and the auditory ossicle, etc., are parts_of the auditory apparatus. The develops_from relationships are transitive: given that the lens develops from the lens placode and the lens placode develops from the sensorial layer, it is implied that the lens develops from the sensorial layer (and more generally from ectoderm). Transitivity operates over is_a relationships as well, e.g. the lens may be inferred to develop from a primary germ layer.
![]()
Xenbase serves as the primary repository and center of development of the XAO 7. The XAO file is freely available at Xenbase's FTP site 14 and is deposited in the OBO Foundry 15.
Ongoing XAO development
Given time and resource constraints, it is unrealistic to incorporate the entire vast body of knowledge about Xenopus anatomy and development, and we assess community input, annotators' needs, and our commitment to meeting good ontology development principles as we prioritize those specific areas of the ontology requiring further curation. Feedback from annotators using the XAO for the EuReGene Gene Expression Database 16, for example, identified embryonic tissue types in need of start- and end-stage information, and we expect that Xenbase's in-house curation of expression data will lead to the addition of new terms and more stage data and definitions to the ontology. Furthermore, some types have only develops_from relationships to other types and need additionally to be classified as subtypes or parts of other structures or tissues. Ideally, every type in the ontology should be assigned one is_a relationship to a supertype, providing the ontology with a clean classification structure and a framework for logical "genus-differentia" type definitions 10. Alignment of the topmost levels of the XAO with CARO provides a basis for achieving this goal: for example, all cell types existing in the ontology have been classified under "cell" (XAO:0003012, CARO:0000013) with several definitions borrowed from the Cell Ontology 17. We plan to collaborate with CARO developers to finish these assignments and to classify structures in additional categories such as "compound organ" and "simple organ" and a variety of tissue types (e.g., epithelium, mesenchyme).
XAO development will also benefit from our collaboration with Amphibian Anatomical Ontology developers and our participation in AAO workshops and ontology curation jamborees. Several XAO types, especially skeletal structures, have names and definitions that are based on the AAO. These types contain cross-references to the amphibian ontology. Further improvement of the skeletal system and the addition of detailed musculature system information to the XAO are near-term projects that will be facilitated by the relationship between our two groups.