BACKGROUND: Previous studies have reported that periderm (the outer ectodermal layer) in zebrafish partially expands into the mouth and pharyngeal pouches, but does not reach the medial endoderm, where the pharyngeal teeth develop. Instead, periderm-like cells, arising independently from the outer periderm, cover prospective tooth-forming epithelia and are crucial for tooth germ initiation. Here we test the hypothesis that restricted expansion of periderm is a teleost-specific character possibly related to the derived way of early embryonic development. To this end, we performed lineage tracing of the periderm in a non-teleost actinopterygian species possessing pharyngeal teeth, the sterlet sturgeon (Acipenser ruthenus), and a sarcopterygian species lacking pharyngeal teeth, the axolotl (Ambystoma mexicanum). RESULTS: In sturgeon, a stratified ectoderm is firmly established at the end of gastrulation, with minimally a basal ectodermal layer and a surface layer that can be homologized to a periderm. Periderm expands to a limited extent into the mouth and remains restricted to the distal parts of the pouches. It does not reach the medial pharyngeal endoderm, where pharyngeal teeth are located. Thus, periderm in sturgeon covers prospective odontogenic epithelium in the jaw region (oral teeth) but not in the pharyngeal region. In axolotl, like in sturgeon, periderm expansion in the oropharynx is restricted to the distal parts of the opening pouches. Oral teeth in axolotl develop long before mouth opening and possible expansion of the periderm into the mouth cavity. CONCLUSIONS: Restricted periderm expansion into the oropharynx appears to be an ancestral feature for osteichthyans, as it is found in sturgeon, zebrafish and axolotl. Periderm behavior does not correlate with presence or absence of oral or pharyngeal teeth, whose induction may depend on 'ectodermalized' endoderm. It is proposed that periderm assists in lumenization of the pouches to create an open gill slit. Comparison of basal and advanced actinopterygians with sarcopterygians (axolotl) shows that different trajectories of embryonic development converge on similar dynamics of the periderm: a restricted expansion into the mouth and prospective gill slits.

• Keywords
• Axolotl, Ectoderm, Gill slits, Mouth, Oropharynx, Periderm, Pharyngeal pouches, Sturgeon, Teeth,
• Publication type
• Journal Article MeSH

Recent years have improved our understanding of the plasticity of cell types behind inducing, building, and maintaining different types of teeth. The latest efforts were aided by progress in single-cell transcriptomics, which helped to define not only cell states with mathematical precision but also transitions between them. This includes new aspects of dental epithelial and mesenchymal stem cell niches and beyond. These recent efforts revealed continuous and fluid trajectories connecting cell states during dental development and exposed the natural plasticity of tooth-building progenitors. Such "developmental" plasticity seems to be employed for organizing stem cell niches in adult continuously growing teeth. Furthermore, transitions between mature cell types elicited by trauma might represent a replay of embryonic continuous cell states. Alternatively, they could constitute transitions that evolved de novo, not known from the developmental paradigm. In this review, we discuss and exemplify how dental cell types exhibit plasticity during dynamic processes such as development, self-renewal, repair, and dental replacement. Hypothetically, minor plasticity of cell phenotypes and greater plasticity of transitions between cell subtypes might provide a better response to lifetime challenges, such as damage or dental loss. This plasticity might be additionally harnessed by the evolutionary process during the elaboration of dental cell subtypes in different animal lineages. In turn, the diversification of cell subtypes building teeth brings a diversity of their shape, structural properties, and functions.

• Keywords
• cell differentiation, dental informatics/bioinformatics, developmental biology, single-cell RNA-seq, stem cell(s), tooth development,
• MeSH
• Regeneration physiology   MeSH
• Tooth * MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

There are several competing hypotheses on tooth origins, with discussions eventually settling in favour of an 'outside-in' scenario, in which internal odontodes (teeth) derived from external odontodes (skin denticles) in jawless vertebrates. The evolution of oral teeth from skin denticles can be intuitively understood from their location at the mouth entrance. However, the basal condition for jawed vertebrates is arguably to possess teeth distributed throughout the oropharynx (i.e. oral and pharyngeal teeth). As skin denticle development requires the presence of ectoderm-derived epithelium and of mesenchyme, it remains to be answered how odontode-forming skin epithelium, or its competence, were 'transferred' deep into the endoderm-covered oropharynx. The 'modified outside-in' hypothesis for tooth origins proposed that this transfer was accomplished through displacement of odontogenic epithelium, that is ectoderm, not only through the mouth, but also via any opening (e.g. gill slits) that connects the ectoderm to the epithelial lining of the pharynx (endoderm). This review explores from an evolutionary and from a developmental perspective whether ectoderm plays a role in (pharyngeal) tooth and denticle formation. Historic and recent studies on tooth development show that the odontogenic epithelium (enamel organ) of oral or pharyngeal teeth can be of ectodermal, endodermal, or of mixed ecto-endodermal origin. Comprehensive data are, however, only available for a few taxa. Interestingly, in these taxa, the enamel organ always develops from the basal layer of a stratified epithelium that is at least bilayered. In zebrafish, a miniaturised teleost that only retains pharyngeal teeth, an epithelial surface layer with ectoderm-like characters is required to initiate the formation of an enamel organ from the basal, endodermal epithelium. In urodele amphibians, the bilayered epithelium is endodermal, but the surface layer acquires ectodermal characters, here termed 'epidermalised endoderm'. Furthermore, ectoderm-endoderm contacts at pouch-cleft boundaries (i.e. the prospective gill slits) are important for pharyngeal tooth initiation, even if the influx of ectoderm via these routes is limited. A balance between sonic hedgehog and retinoic acid signalling could operate to assign tooth-initiating competence to the endoderm at the level of any particular pouch. In summary, three characters are identified as being required for pharyngeal tooth formation: (i) pouch-cleft contact, (ii) a stratified epithelium, of which (iii) the apical layer adopts ectodermal features. These characters delimit the area in which teeth can form, yet cannot alone explain the distribution of teeth over the different pharyngeal arches. The review concludes with a hypothetical evolutionary scenario regarding the persisting influence of ectoderm on pharyngeal tooth formation. Studies on basal osteichthyans with less-specialised types of early embryonic development will provide a crucial test for the potential role of ectoderm in pharyngeal tooth formation and for the 'modified outside-in' hypothesis of tooth origins.

• Keywords
• dermal denticles, ectoderm, endoderm, oropharynx, periderm, pharyngeal denticles, pharyngeal pouches, tooth development,
• MeSH
• Biological Evolution MeSH
• Zebrafish MeSH
• Pharynx * MeSH
• Gills * MeSH
• Germ Layers MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Vertebrate sensory organs arise from epithelial thickenings called placodes. Along with neural crest cells, cranial placodes are considered ectodermal novelties that drove evolution of the vertebrate head. The anterior-most placode generates the endocrine lobe [adenohypophysis (ADH)] of the pituitary, a master gland controlling growth, metabolism, and reproduction. In addition to known ectodermal contributions, we use lineage tracing and time-lapse imaging in zebrafish to identify an endodermal contribution to the ADH. Single-cell RNA sequencing of the adult pituitary reveals similar competency of endodermal and ectodermal epithelia to generate all endocrine cell types. Further, endoderm can generate a rudimentary ADH-like structure in the near absence of ectodermal contributions. The fish condition supports the vertebrate pituitary arising through interactions of an ancestral endoderm-derived proto-pituitary with newly evolved placodal ectoderm.

• MeSH
• Pituitary Gland, Anterior cytology   embryology   MeSH
• Single-Cell Analysis MeSH
• Cell Lineage MeSH
• Zebrafish MeSH
• Endoderm cytology   embryology   MeSH
• RNA-Seq MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Vertebrate dentitions arise at various places within the oropharyngeal cavity including the jaws, the palate, or the pharynx. These dentitions develop in a highly organized way, where new tooth germs are progressively added adjacent to the initiator center, the first tooth. At the same time, the places where dentitions develop house the contact zones between the outer ectoderm and the inner endoderm, and this colocalization has instigated various suggestions on the roles of germ layers for tooth initiation and development. Here, we study development of the axolotl dentition, which is a complex of five pairs of tooth fields arranged into the typically tetrapod outer and inner dental arcades. By tracking the expression patterns of odontogenic genes, we reason that teeth of both dental arcades originate from common tooth-competent zones, one present on the mouth roof and one on the mouth floor. Progressive compartmentalization of these zones and a simultaneous addition of new tooth germs distinct for each prospective tooth field subsequently control the final shape and composition of the axolotl dentition. Interestingly, by following the fate of the GFP-labeled oral ectoderm, we further show that, in three out of five tooth field pairs, the first tooth develops right at the ecto-endodermal boundary. Our results thus indicate that a single tooth-competent zone gives rise to both dental arcades of a complex tetrapod dentition. Further, we propose that the ecto-endodermal boundary running through this zone should be accounted for as a potential source of instruction factors instigating the onset of the odontogenic program.

• Keywords
• axolotl, dental arcades, ectoderm, endoderm, initiation, patterning, tooth development,
• Publication type
• Journal Article MeSH

Despite the wide variety of adaptive modifications in the oral and facial regions of vertebrates, their early oropharyngeal development is considered strictly uniform. It involves sequential formation of the mouth and pharyngeal pouches, with ectoderm outlining the outer surface and endoderm the inner surface, as a rule. At the extreme anterior domain of vertebrate embryos, the ectoderm and endoderm directly juxtapose and initial development of this earliest ecto-endoderm interface, the primary mouth, typically involves ectodermal stomodeal invagination that limits the anterior expansion of the foregut endoderm. Here we present evidence that in embryos of extant non-teleost fishes, oral (stomodeal) formation is preceded by the development of prominent pre-oral gut diverticula (POGD) between the forebrain and roof of the forming mouth. Micro-computed tomography (micro-CT) imaging of bichir, sturgeon and gar embryos revealed that foregut outpocketing at the pre-oral domain begins even before the sequential formation of pharyngeal pouches. The presence of foregut-derived cells in the front of the mouth was further confirmed by in vivo experiments that allowed specific tracing of the early endodermal lining. We show that POGD in sturgeons contribute to the orofacial surface of their larvae, comprising oral teeth, lips, and sensory barbels. To our knowledge, this is the first thorough evidence for endodermal origin of external craniofacial structures in any vertebrate. In bichir and gar embryos, POGD form prominent cranial adhesive organs that are characteristic of the ancient bauplan of free-living chordate larvae. POGD hence seem arguably to be ancestral for all ray-finned fishes, and their topology, pharyngeal-like morphogenesis and gene expression suggest that they are evolutionarily related to the foregut-derived diverticula of early chordate and hemichordate embryos. The formation of POGD might thus represent an ancestral developmental module with deep deuterostome origins.

• MeSH
• Endoderm embryology   MeSH
• Phylogeny MeSH
• Larva genetics   growth & development   MeSH
• Skull embryology   MeSH
• Maxillofacial Development * genetics   MeSH
• X-Ray Microtomography MeSH
• Fishes anatomy & histology   classification   embryology   genetics   MeSH
• Digestive System embryology   MeSH
• Mouth embryology   MeSH
• Gene Expression Regulation, Developmental MeSH
• Tooth embryology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The proper positioning of organs during development is essential, yet little is known about the regulation of this process in mammals. Using murine tooth development as a model, we have found that cell migration plays a central role in positioning of the organ primordium. By combining lineage tracing, genetic cell ablation, and confocal live imaging, we identified a migratory population of Fgf8-expressing epithelial cells in the embryonic mandible. These Fgf8-expressing progenitors furnish the epithelial cells required for tooth development, and the progenitor population migrates toward a Shh-expressing region in the mandible, where the tooth placode will initiate. Inhibition of Fgf and Shh signaling disrupted the oriented migration of cells, leading to a failure of tooth development. These results demonstrate the importance of intraepithelial cell migration in proper positioning of an initiating organ.

• MeSH
• Epithelial Cells cytology   metabolism   MeSH
• Fibroblast Growth Factors metabolism   MeSH
• Mesoderm cytology   metabolism   MeSH
• Molar cytology   embryology   metabolism   MeSH
• Morphogenesis physiology   MeSH
• Mice MeSH
• Odontogenesis physiology   MeSH
• Cell Movement physiology   MeSH
• Gene Expression Regulation, Developmental physiology   MeSH
• Tooth cytology   embryology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Fibroblast Growth Factors MeSH

The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary-developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during gastrulation, which initiates the process and constrains possible evolutionary changes within this area; third, incipient structure of the stomodeal primordium at the anterior neural plate border, where the ectoderm component of the prospective primary mouth is formed; and fourth, the prime role of Pitx genes for establishment and later morphogenesis of oral region both in vertebrates and non-vertebrate chordates.

• MeSH
• Basement Membrane embryology   MeSH
• Biological Evolution * MeSH
• Ectoderm embryology   MeSH
• Phylogeny MeSH
• Vertebrates embryology   MeSH
• Mouth embryology   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH