Key Takeaways & Executive Findings
- •• Molecular developmental evidence supports the revised 'outside-in' hypothesis for fish tooth origin, involving ectodermal scales and endodermal mesenchyme. • Fish dentin is classified into four types: orthodentin, osteodentin, pseudodentin, and vascular dentin, reflecting morphological diversity. • Enameloid mineralization evolved from vesicle-mediated (cartilaginous fish) to collagen-templated (teleosts) mechanisms. • Core signaling pathways (FGF, Shh, Wnt) are functionally conserved but exhibit species-specific regulatory adaptations.
Abstract
BACKGROUND: Fish tooth serves as a pivotal model for depicting evolution and development of vertebrate and human tooth. Recent advancements in molecular developmental biology have provided new insights in the developmental homology between the teeth and scales of fish, as well as the signaling pathways involved. However, comparative studies across species and integration of evolutionary mechanisms require further exploration. OBJECTIVE: To synthesize the evolutionary origins, morphological diversification, and molecular regulatory mechanisms of fish dentition, while critically comparing core propositions and limitations of existing hypotheses. METHODS: A systematic literature search was conducted using PubMed and China National Knowledge Infrastructure databases with search terms “fish teeth, teeth development, evolution of teeth, molecular regulation of teeth” in both English and Chinese. Articles published between 1970 and 2025 were screened. According to the inclusion criteria, 77 articles were ultimately included for comprehensive analysis. RESULTS AND CONCLUSION: Molecular evidence supports the revised “outside-in” hypothesis, confirming that ectodermal scales and endodermal mesenchyme synergistically evolve to form teeth. Fish dentin is classified into four types: orthodentin, osteodentin, pseudodentin, and vascular dentin. In cartilaginous fish, enameloid mineralization is initiated by tubular vesicles secreted by odontoblasts, whereas in teleosts, collagen fibers guide crystal growth, indicating an evolutionary transition from vesicle-mediated to collagen-templated enameloid mineralization. Sonic hedgehog signaling precisely regulates tooth replacement sites in cartilaginous fish, while zebrafish pharyngeal teeth depend on spatiotemporal activation of retinoic acid signaling, confirming functional conservation of core pathways (FGF, Shh, Wnt) but with regulatory mechanisms driven by natural selection, leading to species-specific adaptations.
1. Introduction
Fish, as the earliest extant vertebrates, share a common ancestry with humans within the subphylum Vertebrata. Their teeth serve as a crucial model for understanding the origin and evolution of vertebrate teeth. This review systematically synthesizes the evolutionary origins (the 'inside-out' and 'outside-in' hypotheses), morphological diversification (four dentin types, enameloid mineralization differences), and molecular regulatory mechanisms of fish tooth development. By comparing developmental patterns between cartilaginous and bony fishes, we aim to refine evolutionary models and provide a theoretical basis for regenerative research.
The study of fish teeth not only illuminates the evolutionary history of vertebrate dentition but also offers insights into the conserved molecular pathways governing tooth development. Recent advances in molecular developmental biology have revealed the developmental homology between teeth and scales, as well as the involvement of key signaling pathways. However, comparative studies across species and the integration of evolutionary mechanisms remain incomplete. This review addresses these gaps by critically evaluating existing hypotheses and synthesizing current knowledge on the molecular regulation of fish tooth development.
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WANG Shuoran, HUANG Rui, DONG Lingyue, AN Wei, HUANG Xiaofeng (2026). Evolution, development and molecular regulation of fish tooth. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21321
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Frequently Asked Questions
What are the two main hypotheses for the evolutionary origin of fish teeth?
The two main hypotheses are the 'inside-out' theory, which proposes that teeth originated from endodermal pharyngeal structures and migrated to the oral cavity, and the 'outside-in' theory, which suggests that teeth evolved from ectodermal body scales that internalized through gill slits. The revised 'outside-in' hypothesis emphasizes the synergistic interaction between ectodermal odontogenic tissue and endodermal mesenchyme.
How is fish dentin classified?
Fish dentin is classified into four types: orthodentin, osteodentin, pseudodentin, and vascular dentin, based on structural and developmental characteristics.
What are the key signaling pathways involved in fish tooth development?
Key signaling pathways include fibroblast growth factor (FGF), sonic hedgehog (Shh), and Wnt. These pathways are functionally conserved across species but exhibit species-specific regulatory adaptations.
What is the significance of studying fish teeth for human dental research?
Fish teeth serve as a model for understanding vertebrate tooth evolution and development, providing insights into conserved molecular mechanisms that may inform regenerative approaches for human dental tissues.
What are the limitations of current research on fish tooth evolution?
Limitations include the incomplete fossil record, which hampers definitive conclusions about tooth origin, and the lack of direct experimental evidence for the 'outside-in' hypothesis in fish, as much of the evidence comes from non-fish models like salamanders.
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