Review Old, New and New-Old Concepts About the Evolution of Teeth by P

Review Old, new and new-old concepts about the evolution of teeth By P. E. Witten1, J.-Y. Sire2 and A. Huysseune1

1Research Group ‘Evolutionary Developmental Biology’, Biology Department, Ghent University, Gent, Belgium; 2UMR 7138, Universite Pierre et Marie Curie, Paris, France

Summary cap. On the body surface they were transformed into The evolutionary origin of teeth from dermal denticles odontocomplexes, from which arose various types of scales (odontodes) that developed in the mouth cavity, designated (Huysseune and Sire, 1998; Sire et al., 2009). In chondrichth- as outside-in hypothesis, has long been undisputed. The out- yans, individual odontodes are still present as dermal side-in hypothesis is based on the conclusion that dermal denticles (also called placoid scales) (Hall and Witten, 2007). denticles and teeth fulfil the criteria of homology in an exem- Development of teeth and dermal denticles requires interac- plary manner. Over the past 15 years, this hypothesis has tions between the epithelium and the underlying mesenchyme been challenged. Proponents of the alternative inside-out (see also Hall, 2014; in this volume). Also the developmental hypothesis suggest that teeth did not evolve from dermal pathways that produce these structures are highly conserved denticles, that they are of endodermal origin (forming in con- (Miyake et al., 1999; Sharpe, 2001; Debiais-Thibaud et al., junction with neural crest-derived mesenchyme) and that they 2011). The sequence of appearance of odontodes and teeth in evolved several times independently in different lineages of the fossil record and the shared characters that establish the vertebrates. Key arguments for the inside-out hypothesis are homology between teeth and odontodes are the basis for the mineralized structures of conodonts that are accepted as classical hypothesis, according to which teeth derive from teeth, the exclusive acceptance of placoderm pharyngeal den- odontodes that developed in the oral cavity when the jaws ticles as teeth, together with the rejection of the presence of formed in early gnathostomes (Hertwig, 1874; Ørvig, 1967; teeth in basal placoderms. We summarize the results of Reif, 1982; Smith and Hall, 1990). This view is also desig- recent studies that have been triggered by the fruitful discus- nated as the outside-in hypothesis (Blais et al., 2011). sion between the two conflicting hypotheses. New findings Phrased in a more developmental way, teeth derive from support the traditional outside-in hypothesis: the mineralized odontogenically competent ectoderm that expanded into the elements of conodonts are not teeth, and the oral cusps in mouth cavity and interacted with competent neural crest- basal placoderms are true teeth. Furthermore, new develop- derived mesenchyme. This ectoderm could then have trans- mental and molecular data clarify homology between teeth ferred its odontogenic competence to endoderm as suggested € and dermal denticles. Today a new synthesis is emerging by Huysseune et al. (2009, 2010) (Fig. 1). Rucklin et al. about the evolutionary origin of teeth from dermal denticles (2011, 2012) endorse the idea that, ultimately, teeth and and about the unity of the elements of the dermal skeleton. other oral and pharyngeal denticles must be derived through the extension of the odontogenic capacity of the external dermis to the internal dermis and endoderm. The classical view about the origin and evolution of teeth Teeth are highly conserved elements of the vertebrate skeleton. Notwithstanding some examples of derived tooth types An alternative view on the evolution of teeth (see e.g. Huysseune and Sire, 1998; Davit-Beal et al., 2009; The long-time undisputed outside-in hypothesis on the evolu- Sire et al., 2009), teeth in all toothed vertebrates are made tionary origin of teeth has been challenged in a series of pub- from dentine and covered by a hypermineralized cap. Inside lications that suggested that (i) teeth evolved more than they have a pulp cavity that is vascularized and innervated once, and (ii) teeth evolved independent from odontodes in (Sire and Huysseune, 2003). These principal characters of the pharynx of ancient vertebrates and (iii) are thus of endo- teeth are shared with the basic units of the dermal skeleton, dermal origin (Smith and Coates, 1998; Smith and Johanson, the odontodes (De Beer, 1928; Ørvig, 1977; Reif, 1982; Smith 2003; Fraser et al., 2009; Fraser and Smith, 2011). The con- and Hall, 1990; Janvier, 1996; Huysseune and Sire, 1998). jecture that pharyngeal teeth could have evolved prior to oral Odontodes were mineralized elements of the dermal skeleton teeth and expanded into the mouth cavity led to a new that were present in the first, jawless, vertebrates (Donoghue hypothesis, designated as the inside-out hypothesis (Fraser and Sansom, 2002). Odontodes are made of dentine sur- and Smith, 2011) (Fig. 1). The inside-out hypothesis builds rounding a pulp cavity and covered by an hypermineralized on a number of postulates:

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which teeth (or structures interpreted as teeth) appear in the fossil record, is taken as evidence that teeth evolved multiple times in vertebrates (Smith, 2003).

Two conflicting hypotheses The inside–out hypothesis was never undisputed. Opponents do not accept conodont mineralized structures as teeth, refuse the idea about a multiple origin (convergent evolution) Fig. 1. Schematic representation of the outside-in and the inside-out of teeth, and emphasize the firmly established homology of hypothesis for the evolution of teeth. The outside-in hypothesis as odontodes and teeth (Burrow, 2003; Sire and Huysseune, rephrased by Huysseune et al. (2009, 2010) postulates that ectoderm- derived odontodes invaded the mouth and the pharyngeal cavity, via 2003; Reif, 2006; Huysseune et al., 2009). Clearly, an ongo- the mouth openings and via different branchial openings. Eventually, ing productive debate about the developmental and evolu- ectoderm-derived odontogenic competence could have been trans- tionary origin of teeth has triggered several studies, all of ferred from ectoderm to endoderm (co-option). Intermediate stages which challenge the above listed postulates of the inside-out between dermal denticles and teeth in proximity to jaw margins further support the idea that tooth and dermal denticles are homolo- hypothesis and support the classical outside-in hypothesis gous. The inside-out hypothesis postulates the parallel evolution of (Huysseune et al., 2009; Turner et al., 2010; Blais et al., teeth and dermal denticles. According to this hypothesis, teeth 2011; Rucklin€ et al., 2011, 2012; Murdock et al., 2013; Qu evolved in the endoderm-covered oropharyngeal cavity. The postu- et al., 2013). Thanks to this fruitful debate, a refined under- lated parallel evolution of teeth in conodonts and in placoderms, as standing of the evolution of dermal denticles and teeth is well as the assumed lack of intermediate stages between dermal denticles and teeth have been quoted to support the inside-out hypothe- emerging. We here summarize the results of the recent sis. Developmental data in extant vertebrates that show tooth studies. development in ectoderm-covered and in endoderm-covered locations are differently interpreted by the proponents of the two conflicting hypotheses. Both hypotheses accept co-option. Red arrows indicate Mineralized conodont elements are not teeth the postulated direction of tooth expansion in evolution. Blue represents ectoderm and ectoderm-derived skeletal structures, dermal den- Two papers published by a group of prominent palaeontolo- ticles and teeth. Green represents endoderm as well as the proposed gists in 2010 re-evaluated conodont characters and the phylo- endoderm-derived teeth. This cartoon was inspired by Huysseune genetic position of conodonts (Blieck et al., 2010; Turner et al. (2009), and from figures published Fraser et al. (2010), and et al., 2010). The authors conclude that conodonts are not Blais et al. (2011). vertebrates, possibly not even chordates. Blieck et al. (2010) emphasize the lack of fossil material that supports the popu- 1 Conodonts are accepted as vertebrates and mineralized lar reconstruction of conodont animals, eel-like vertebrates conodont structures have been accepted as teeth (Don- with huge, unprotected eyes in front of a snout. Conodonts oghue and Sansom, 2002). These ‘teeth’ are believed to are removed by these authors from the vertebrate tree be located inside a pharynx (Donoghue et al., 2000). because of the extreme low level of cephalisation, the lack of Consequently, conodont ‘teeth’ are assumed to be endo- a dermal skeleton or any other vertebrate skeletal tissue such derm-derived. Since conodonts lack a dermal skeleton, as cartilage, and the lack of segmentally arranged paraxial the first vertebrate tooth-like structures would have elements. The conodont trunk musculature is simple V- evolved before odontodes (Johanson and Smith, 2005). shaped and not W-shaped as it is the case for vertebrates. 2 In Placodermi, the most basal clade of jawed vertebrates, Most important for the evolution of teeth, the conodont and also in Chondrichthyes, the arrangement of ecto- mineralized structures contain a large-crystal, albid material derm-derived dermal denticles indicates the lack of a den- (also called white matter, an essentially opaque formless tis- tal lamina. Following a definition of Reif (1982), sue, characterized by voids) that is neither dentine nor odontode-derived structures that develop without a dental enamel nor enameloid. Their growth is continuous, and they lamina are not accepted as teeth. Consequently, in placo- could have functioned in a way similar to the feeding appa- derms, only pharyngeal, but not oral, denticles are ratus of some non-vertebrates, such as polychaete annelids accepted as teeth. These teeth are again assumed to be of (Turner et al., 2010). The latter authors endorse the analysis endodermal origin (Smith and Coates, 1998; Smith, 2003; of Reif (2006) who emphasized that there is no way to Johanson and Smith, 2005). homologize odontodes and teeth with conodont elements on 3 If structures are homologous one would expect to find the basis of fabric, of structure, of topological relationship, transitory stages between these structures during develop- of inferred developmental tissue relationship, of histogenetic ment and/or in the fossil record. It is suggested that tran- principles and of a morphogenetic program. Superficially, sitory stages between endoderm-derived teeth and conodont elements can resemble small fish teeth, but cono- ectoderm-derived dermal denticles are lacking (Smith and dont elements can be morphologically indistinguishable from Coates, 1998; Johanson and Smith, 2005). serrated mineralized fossil annelid structures (Marshall et al., 4 The assumed phylogenetic relationships between con- 2013). Different from Turner et al. (2010) and Reif (2006), odonts, placoderms and eugnathostomes (jawed verte- Murdock et al. (2013) emphasize that there are structural brates except placoderms), and the inferred sequence in similarities between vertebrate odontodes and euconodont 638 P. E. Witten, J.-Y. Sire and A. Huysseune mineralized elements. Still, the authors agree that eucon- and structure of oral cusps in placoderms clearly reveals cor- odont elements are not teeth but an example of convergence. respondence with odontodes and teeth. Rucklin€ et al. (2012) Whether conodonts are vertebrates, chordates, or not even and Giles et al. (2013) conclude that the teeth that they iden- chordates, is still a matter of controversy (Purnell et al., tify in the earliest jawed vertebrates are homologous to the 2013). Within the context of this review, it is important to teeth of crown gnathostomes and, as a consequence, that point out that those scientists that support the idea that eu- teeth did not evolve convergently among extant and extinct conodont animals are vertebrates, agree that mineralized classes of early jawed vertebrates. The homology of teeth conodont elements are unrelated to dermal denticles or teeth. and dermal denticles is also supported by a recent analysis of Conodont elements are now regarded as feeding structures developmental stages of fossil acanthodians with phase con- analogous to structures encountered in vertebrates and non- trast X-ray Synchrotron microtomography (PPC-SRmCT). vertebrates (Murdock et al., 2013). The removal of conodont This study also shows a dentition-like patterning of dermal elements from the list of odontode/tooth-related structures denticles (Qu et al., 2013). Confirming that the mechanism of removes a cornerstone of the inside-out hypothesis. odontode (denticle) development corresponds to that of gnathostome teeth, Qu et al. (2013) further argue for the homology of teeth and dermal denticles and refute the idea that Oral denticles of placoderms have tooth characters oropharyngeal elements and external odontodes are funda- In addition to mineralized conodont structures, the inside- mentally different. Indeed, the enormous diversity of dermal out hypothesis refers to tooth whorls located in the pharynx denticles and tooth patterning in extinct and extant verte- of thelodonts (jawless vertebrates) as a second example that brates (Huysseune and Sire, 1998; Sire and Huysseune, 2003; teeth evolved ‘inside’, in an endoderm-lined setting, and were Witten et al., 2005; Sire et al., 2009) invalidates arguments subsequently co-opted to colonise the jaw margins ‘inside- about convergent evolution of teeth and dermal scales that out’ (Smith and Coates, 1998). These oropharyngeal denticle refer to different patterns. Moreover dermal scales and teeth whorls are accepted as teeth based on the assumption that are developmental modules (Stock, 2001; Donoghue and their patterning suggests successional development and thus Sansom, 2002; Johanson et al., 2008). If these modules development from a dental lamina. Huysseune et al. (2009, acquire a new function as teeth inside the oral cavity, it is 2010) agreed with their identification as teeth, but at the safe to assume that their patterning changes together with same time pointed out that their location is consistent with the new function. an ectoderm-derived origin. Denticles covering the postbran- chial lamina in placoderms likewise have been assigned a ‘tooth’ status based on their inferred ordered addition (Jo- The many shapes of the dental lamina hanson and Smith, 2005). As is the case for thelodonts, this The dental lamina is a thickened band of epithelial tissue location is an area where invagination of ectoderm could that initiates tooth development by making contact with have carried odontogenic competence deep into the body competent mesenchyme. Subsequently, the epithelium differ- (Huysseune et al., 2009, 2010). Rucklin€ et al. (2012) have entiates into the outer and inner dental epithelium. The latter since demonstrated that the tooth-like structures on the post- provides ameloblasts that secrete enamel. The mesenchyme branchial lamina of placoderms are merely focal develop- provides odontoblasts that produce the dentine matrix (De ments of continuous sheets of spongy bone. Beer, 1928; Huysseune and Sire, 1998; Tucker and Sharpe, Denticles located in the skin and internal oral mucosa in 2004). In vertebrates with repeated tooth replacement the basal placoderms are considered by Smith and Johanson dental lamina can be continuous or discontinuous, and per- (2003) to develop synchronously and thus without a dental manent or non-permanent (Reif, 1982). For example, a dis- lamina, and are therefore not accepted as teeth. Smith and continuous and non-permanent dental lamina can arise anew Johanson (2003) furthermore identify ‘true teeth’ based on from the outer dental epithelium of a more developed tooth their regulated addition in association with the gnathal bones at the time it will be replaced (successional dental lamina, in advanced, but not in basal placoderms. This led them to Huysseune and Thesleff, 2004). Reif (2006) suggested that suggest that teeth are the result of convergent evolution. Bur- development from a dental lamina distinguishes teeth from row (2003) has disputed the denial of tooth-like structures on other odontode-derived elements. Although the dental lamina the jaw bones in basal placoderms, showing staggered rows is not preserved in the fossil record, its presence or absence of tubercles on the gnathals in basal placoderms, similar to (inferred from the pattern of candidate tooth structures) the structures in advanced placoderms, interpreted by Smith plays an important role in the discussion if denticles in the and Johanson (2003) as teeth. A recent analysis of placoderm oropharyngeal cavity are accepted as teeth. For example, a gnathal ossifications with Synchrotron X-ray Tomographic suggestion about the independent evolution of teeth in the Microscopy (SRXTM) supports Burrow’s view (Rucklin€ placoderm group Arthrodira recognizes structures located on et al., 2012). The examination of a developmental series of a placoderm gnathal plates as teeth, also because their arrange- placoderm (Compagopiscis croucheri, Arthrodira) clearly ment suggests the presence of a dental lamina (Smith and Jo- shows oral tooth cusps that develop successionally (not syn- hanson, 2003; Johanson and Smith, 2005). Conversely, the chronous). The cusps are composed of dentine, and have dis- tooth status of oral cusps in less derived placoderm groups is tinct pulp cavities. Pulp cavities are lined with centripetally not recognized since their arrangement does not indicate the nested tissue layers permeated by radially arranged and polar- development from a dental lamina. The in-depth structural ized canaliculi, typical of dentine tubules. Such arrangement analysis of oral cusps in Arthrodira by Rucklin€ et al. (2012) The evolution of teeth 639 confirms their tooth status. These authors, however, point Tucker in London used endoderm labelling in a Sox17-2A- out that, based on their structural criteria, the oral cups in iCre/Rosa26 reporter mouse. Their study revealed that endo- other placoderm groups can be recognized as teeth as well. derm has no contribution to tooth development at any stage This, and data that indicate that Arthrodira are close rela- of development. In the mouse all teeth, including the last tives of chondrichthyans and osteichthyans, led these authors molar, are entirely ectoderm-derived (Rothova et al., 2012). to conclude that placoderm teeth did not evolve indepen- Development is often conserved, but not always. Thus we dently from gnathostome teeth. We like to emphasize that can not know for sure whether processes of tooth develop- living jawed vertebrates show a great diversity in epithelial ment in the axolotl or in the mouse are conserved or connectivity between predecessor and successor. In Atlantic derived. The mouse experiments by Rothova et al. (2012) salmon, for example, functional teeth and replacement teeth provide, however, precise identification of endoderm and develop in such close apposition that a dental lamina cannot solve the question about the possible contribution of endo- be recognized as a distinct strand of epithelial tissue. Still, derm to mouse tooth development (Tucker and Sharpe, replacement teeth develop from the outer dental epithelium 2004). In carp, that have only pharyngeal teeth, ectoderm of the predecessor tooth (Huysseune et al., 2007; Huysseune penetrates inwards into the presumptive pharyngeal slits of and Witten, 2008). The same situation is observed in the the embryos and covers the endoderm, as observed by basal bony fish Polypterus senegalus (De Clercq et al., 2014, Edwards (1929). In fossil temnospondyl amphibians, pharyn- in this volume). Such an intimate connection between prede- geal teeth disappear together with the disappearance of the cessor and replacement tooth could well explain the arrange- gill openings (Schoch, 2002). These findings led Huysseune ment of oral denticles in placoderms. et al. (2009, 2010) to suggest that during evolution tooth development did depend on competent ectoderm invading the oropharyngeal cavity via the mouth opening and via the Dermal denticles inside the oral cavity gill slits, or rather via ectoderm-endoderm contacts preceding There is little doubt that the developmental mechanisms that the formation of the slits. They coined the term ‘modified produce dermal denticles and teeth are essentially identical outside-in’ for this hypothesis. Development evolves (Hall, (Debiais-Thibaud et al., 2011). Correspondence between 2005) and thus one can speculate that the odontogenic com- teeth, dermal denticles and various scales is also established petence of ectoderm can be transferred to endoderm by co- for their structure, microstructure and cellular composition option. This can explain observations of teeth that develop (De Beer, 1928; Miyake et al., 1999; Sire and Huysseune, from an endoderm-covered lining in extant vertebrates. 2003). Also, mutation of ectodysplasin (EDA) or of its Regarding the principle of co-option of odontogenic compe- receptor (EDAR) in zebrafish selectively affects skeletal ele- tence (Smith, 2003; Fraser et al., 2004), there is thus an ments evolutionarily derived from ectoderm: fin rays and agreement between the proponents of the inside-out and the scales, as well as pharyngeal teeth (Harris et al., 2008; Har- outside-in hypotheses. ris, 2012). Obviously, there is little leeway for arguing against the common descent of dermal denticles, scales and teeth from the odontodes that were present on the body sur- Intermediate stages between dermal denticles and teeth face of early, jawless vertebrates. If, however, teeth in extant An argument raised to dispute the homology of dermal den- vertebrates develop from endoderm, could that prove that ticles and teeth is the supposed lack of morphologically odontodes, dermal denticles and teeth are not homologous? intermediate forms between dermal denticles and teeth Darwin was convinced that embryonic development and lar- located in the oropharyngeal cavity (Smith and Coates, val stages show us, more or less completely, the condition of 1998). Indeed, if a dermal element (i.e. odontode) becomes the progenitor of the whole group in its adult state (Darwin, modified in the course of evolution, one expects to find 1859, p. 345). Ever since, and despite vivid debates about intermediate stages (Hall and Kerney, 2012). Different from the extent of validity of this concept, scientists analyze devel- what the inside-out hypothesis assumes, intermediate stages opment also to obtain insights into evolution (von Baer, exist (Botella et al., 2007). Daniel (1934) describes the transi- 1828; Haeckel, 1866; Gould, 1977; Raff, 1996; Hall, 1998). tion of placoid scales (= dermal denticles) into teeth in the Likewise, ontogeny is also studied to elucidate the relation- extant shark of the genus Heptanchus. A recent study by ship between dermal denticles and teeth (Donoghue, 2002). Blais et al. (2011) shows intermediate forms between head Teeth that develop deep inside the oral cavity and pharyn- scales and teeth in an early Devonian eugnathostome geal teeth are often assumed to be of endodermal origin (Acanthodian). According to Blais et al. (2011) scales that (Jackman et al., 2004; Fraser and Smith, 2011). For the develop in closer proximity to the mouth are modified and Mexican axolotl (Ambystoma mexicana) and for mice it has become extremely tooth-like. Moreover, in every detail the been suggested that only teeth at the jaw margins derive similarity of these scales to teeth suggests that the two ele- from ectodermal epithelium (Tucker and Sharpe, 2004; ments are the result of the same developmental processes, Soukup et al., 2008; Ohazama et al., 2010). In mammalian indicative for the existence of a field of gene expression near embryos, the epithelium located posterior to the buccopha- the mouth margin in which scales can be transformed into ryngeal membrane is viewed to be endoderm (see review by teeth. The presence of extra-oral teeth in several teleost spe- Soukup et al., 2013). Teeth that develop posterior to the cies (Arratia, 1990; Sire, 2001; Sire and Allizard, 2001) buccopharyngeal membrane should thus be endoderm- further demonstrates the existence of a field of odontogenic derived. However, a recent study from the laboratory of A. gene expression outside the mouth margin in extant 640 P. E. Witten, J.-Y. Sire and A. Huysseune vertebrates. Blais et al. (2011) conclude from their studies Hegelian dialectics: thesis-antithesis-synthesis that their unequivocal example for transitional forms Paleontological, developmental, morphological, structural, between dermal scales and teeth removes one of the chief biochemical and molecular data strongly support the homol- objections to the outside-in hypothesis for the origins of ogy of dermal denticles and teeth. Still, the unity of dermal teeth in jawed vertebrates. denticles and teeth has been challenged during the last 15 years. The discussion about the more recent inside-out hypothesis and the traditional outside-in hypothesis has trig- Outside-in against inside-out: the different use of the homology gered several studies, all of which provide evidence for the concept original outside-in hypothesis, for the unity of teeth, odon- Homology is the hierarchical foundation of all biology and todes and dermal denticles. The argument that dermal denti- we invoke homology whenever we compare two or more cles and teeth lack intermediate stages has been refuted by biological units (Hall, 2003). The discussion about the evo- Blais et al. (2011) who demonstrate tooth-like scales in early lutionary origin of teeth reveals a different use of the Devonian eugnathostomes. The argument that fundamentally homology concept. Comparative anatomists and embryolo- different patterning mechanisms establish positions of teeth gists established the homology concept in pre-Darwinian and dermal denticles has been rejected (Qu et al., 2013). times. Eventually the evolutionary theory was able to pro- Huysseune et al. (2009, 2010) and Rucklin€ et al. (2012) have vide a rational explanation for the existence of homologous emphasized that one should not remove the tooth-status structures (Hall, 2014; in this volume). Subsequently, based from oral teeth based on the assumed lack of a dental lam- on the diagnosis of homology, it was possible to establish ina. Consequently, the identification of oral cusps in placo- phylogenetic trees (Brigandt and Griffiths, 2007). It has derms by Rucklin€ et al. (2012) as teeth opposes the been a valid approach since to investigate the homology of argument that teeth derive from endodermal pharyngeal two characters without being upfront interested in cladoge- tooth whorls. The now undisputed fact that conodont miner- netic relationships (Schmitt, 1989). Molecular biologists that alized elements are unrelated to vertebrate teeth and dermal extend the homology concept to proteins and genes have denticles (Murdock et al., 2013) has removed another argu- followed this approach (Griffiths, 2007). Homology is estab- ment for an endodermal, and dermal skeleton-independent, lished based either on operational criteria or on a taxic evolution of teeth (Turner et al., 2010). Mechanisms by conception (Griffiths, 2007). The operational criteria regard which ectoderm-derived teeth can acquire a pharyngeal posi- organs or structures as homologous with increasing cer- tion have been proposed by Huysseune et al. (2009, 2010). In tainty (i) if they share the position in relation to other hindsight it appears that the discussion about the origin of structures, (ii) if they share specific qualities (e.g. micro- teeth went through a complete round of Hegelian dialectics. structure, biochemical composition, gene expression pat- We believe that the origin of teeth from dermal denticles terns) and (iii) if intermediate stages exist, be it ontogenetic (odontodes) is again firmly established. Thus, there is also no or phylogenetic (Remane, 1952; Futuyma, 1998; Ridley, need for the assumptions that teeth may have evolved con- 2004; Zachos and Hoßfeld, 2006; Schultze and Arratia, vergently from endodermal and from ectodermal locations 2013). Homologous structures need not meet all criteria. (‘inside and out’, Fraser et al., 2010; Fraser and Smith, Homologous structures can develop through different path- 2011). The past discussion about the origin of teeth in verte- ways because development evolves (Hall, 2003). Intermedi- brates has, however, triggered exciting and ongoing research ate stages can be lacking because the fossil record is about the mechanisms of tooth development, replacement incomplete (Hall and Kerney, 2012). The position of a and patterning. structure in relation to other structures can change. For example, pelvic fins of advanced teleost fish are now located in front of the pectoral fins (Drucker and Lauder, 2002). Acknowledgements Teeth and dermal denticles are, however, arguably prime We are very thankful to Brian K. Hall (Dalhousie Univer- examples for structures that meet operational homology cri- sity, Halifax, Canada) and Philip C. J. Donoghue (University teria. The idea underlying the taxic concept of homology of Bristol, UK) for reviewing this manuscript and for provid- has been summarized by Wake (1999, 2003): homology is ing insightful advice for improvements. The final manuscript not evidence for evolution. Homology is the anticipated remains of course entirely the responsibility of the authors. and expected consequence of evolution. Support for the inside-out hypothesis is drawn from the taxic homology concept. A cladistic analysis that, for example, assigns con- References odonts to the vertebrates or even to the gnathostomes is Arratia, G., 1990: Development and diversity of the suspensorium of regarded as valid evidence that teeth evolved prior to the trichomycterids and comparison with loricarioids (Teleostei, Si- luriformes). J. Morphol. 205, 193–218. dermal skeleton, more than once, and are not homologous € to odontodes (Smith, 2003). Adherents of the outside-in von Baer, K. E., 1828: Uber Entwicklungsgeschichte der Thiere: Beobachtung und Reflexion. Bei den Gebrudern€ Korntrager,€ hypothesis argue that based on operational criteria, homol- Konigsberg.€ 271 pp. ogy between teeth and odontodes is firmly established. Blais, S. A.; MacKenzie, L. A.; Wilson, M. V. 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