‘Monster… -omics’: on segmentation, re-segmentation, and vertebrae formation in amphibians and other vertebrates
© Buckley et al.; licensee BioMed Central Ltd. 2013
Received: 1 October 2012
Accepted: 2 April 2013
Published: 11 April 2013
The axial skeleton is one of the defining evolutionary landmarks of vertebrates. How this structure develops and how it has evolved in the different vertebrate lineages is, however, a matter of debate. Vertebrae and vertebral structures are derived from the embryonic somites, although the mechanisms of development are different between lineages.
Using the anecdotal description of a teratological newt (Triturus dobrogicus) with an unusual malformation in its axial skeleton, we review, compare, and discuss the development of vertebral structures and, in particular, the development of centra from somitic cellular domains in different vertebrate groups. Vertebrae development through re-segmentation of the somitic sclerotomal cells is considered the general mechanism among vertebrates, which has been generalized from studies in amniotic model organisms. The prevalence of this mechanism among anamniotes is, however, controversial. We propose alternative developmental mechanisms for vertebrae formation that should be experimentally tested.
Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates, foundations that should expand the extent of future comparative studies. Although immersed in the ‘-omics’ era, we emphasize the need for an integrative and organismal approach in evolutionary developmental biology for a better understanding of the causal role of development in the evolution of morphological diversity in nature.
Teratologies recurrently occur in all animal groups. Although generally considered incidental natural curiosities, they reflect intrinsic properties of developmental systems. Not every imaginable ‘monster’ is possible: similar to non-aberrant morphological variants, teratologies appear in nature in a discrete manner. If all of the normal and aberrant shapes found in a group were plotted in a geometrical space, thus constructing a theoretical ‘morphospace’, the resulting points would not be scattered all along the plot but would concentrate around specific areas. These areas would be defined by the characteristics of the developmental system of the group. This idea of monsters as ‘logical developmental entities’ is rooted in classic morphological  and modern developmental  studies. Teratologies are not random: they result from the truncation or alteration of specific developmental pathways. Therefore, the study of these alterations may reveal veiled or cryptic underlying processes involved in the generation of form . In this study, we use the anecdotal description of the axial skeleton of a teratological individual of the Danube crested newt (Triturus dobrogicus) to review and discuss the developmental processes of segmentation, re-segmentation, and vertebrae formation in vertebrate lineages. Vertebrae development through re-segmentation of the somitic cellular domains is considered the general mechanism among vertebrates, but its occurrence in anamniotes is controversial. We propose alternative mechanisms of vertebrae development that should be experimentally tested in anamniotes. Furthermore, in this ‘-omics’ era, we stress the need for an organismal approach in evolutionary and developmental biology to better understand the causal role of development in the evolution of morphological diversity in nature.
Segmentation, somites, and vertebrae formation
Developing embryonic somites, however, are not homogeneous structures. Following differentiation, they become polarized and compartmentalized, leading to several cellular domains that develop into different axial elements (e.g. muscles, ribs, rib bearers, centra) . The dorsolateral half of the somites, for instance, forms the dermomyotome, which eventually differentiates into dermis and muscles. A space or cavity, called the myocoel, separates this domain from the ventromedial half of the somites. Cells from this later area form the sclerotome, which is the cellular precursor of the vertebral elements such as the centra, ribs and rib bearers. The sclerotome is also rostrocaudally polarized, with the two cellular sclerotomic subdomains being separated by the so-called sclerocoel.
As a general mechanism among vertebrates, sclerotome cells delaminate from the somites and form a thin unsegmented layer around the notochord (the perichordal tube) (Figure 1B) . These cells then aggregate and form perichordal rings around the notochord approximately at the level of the middle of each somite (Figure 1C). Sclerotome cells also aggregate at somites boundaries either (i) dorsally, along the sides of the neural tube, eventually developing into vertebral neural arches, or (ii) ventromedially, forming the rudiments of the distal part of the ribs. Perichordal rings give rise to the intervertebral joints, and the area between them forms the centra (vertebral bodies), which align with the intersegmental neural arch rudiments. Therefore, neural arches, centra, and the distal part of the ribs develop at the intersomitic boundaries, but from different sclerotomal cell precursors and at different times.
The formation of centra differs among vertebrate lineages. In amniotes, for instance, centra, which form at somite boundaries, result from the migration of cells from the caudal half of one sclerotome and the rostral half of the sclerotome of the adjacent somite (Figure 1C,D) . Therefore, amniotic vertebrae do not reflect the primary segmentation pattern (i.e., original somite location); rather, they are located intersegmentally and result from the redistribution of sclerotomal cells in a process known as re-segmentation.
The genetic control of segmentation and re-segmentation has been extensively studied in amniotes such as mouse and chick, leading to the general view that similar processes occur in all vertebrate lineages, which is not necessarily true. Although vertebrae are located intersegmentally in all vertebrates, it is unclear whether the active migration of cells from adjacent somites to form the centra is general among lineages. Re-segmentation in anamniotes is controversial. In some teleosts, a ‘leaky’ re-segmentation occurs in which centra are formed from cells originated from several somites . Furthermore, the development of centra in other teleost lineages is strongly influenced by molecular signaling and cellular contribution from the notochord [18, 19]. In fact, five different modes of centra formation have been described for teleosts .
In amphibians, somitogenesis has been thoroughly characterized in classic embryological studies [16, 21], but the cellular and morphogenetic processes and the genetic and molecular mechanisms involved during amphibian vertebral segmentation are largely unknown for this group (with the exception of Xenopus and Ambystoma). Moreover, the evidence for re-segmentation in amphibians is equivocal. The sclerotome in salamanders and frogs is apparently reduced in cell number and not polarized rostro-caudally. Furthermore, no clear presence of sclerocoel has been shown in these two groups. The scant sclerotomal cell population forms late during development, and the developmental fate of these cells is unclear. It has been suggested, however, that there is no active movement of cells from adjacent sclerotomes to form the vertebrae centra [22–24]. In limbless amphibians (Gymnophiona), nevertheless, re-segmentation has been reported. In this case, the sclerotome is more developed and rostro-caudally polarized in two halves, separated by a sclerocoel; re-segmentation may have independently evolved in this lineage to distribute this larger cell population .
From the anecdotic observation of a rather unusual vertebral malformation in an individual of the newt Triturus dobrogicus (Amphibia, Caudata, Salamandridae), we discuss what is known (or assumed) about the developmental mechanisms and evolutionary patterns underlying vertebrae formation in the different vertebrate lineages.
Insights from the ‘monster’
The causal origin of the malformation is difficult to assess. This is a rather unusual phenotype, especially concerning the asymmetric distribution of ribs in the fused or enlarged centra, which, as far as we know, has not been previously reported in the literature. To our knowledge, no mutant studies have revealed similar phenotypes or malformations like the one described here. The teratology could have a genetic or epigenetic nature and thus related either to mutations or to the exposure of exogenous teratogenic agents during development, respectively . Several genetic pathways have been shown to be critical during somite and vertebrae development. Hox genes are known to be directly involved in somite and vertebrae formation and, thus, could be involved in the teratology. Hox gene mutations and mis-expression, however, lead most frequently to homeotic transformations, which are not observed this case. Mutations in regulatory and signaling genes have also been related to various vertebral syndromes and aberrant phenotypes [29, 30]. For example, the signaling molecule retinoic acid (RA) is involved in left-right symmetry of somite formation . The disruption of the RA signaling pathway may lead to various syndromes involving symmetry defects on the vertebral axis, which could also be related to the pattern observed in this study.
Interestingly, the anomaly reported here occurs in the last trunk vertebrae. It has been suggested that the anterior trunk region is much more conservative in terms of potential variability than the posterior part of the axis . Furthermore, in a population survey of the plethodontid urodele Batrachoseps, Jockusch  reported a high incidence of developmental abnormalities in vertebrae at the thoracic/sacral region, including asymmetric pelvis articulations and insertion of one or more extra half vertebrae on only one side of the vertebral axis. Furthermore, the final number of trunk vertebrae was not specified until late in development. This has also been shown for other salamander species that have the capacity to add segments to their tails (i.e., vertebrae) post-embryonically, at adult stages . The number of embryonic somites, thus, would not specify the final number of vertebrae. This is interesting since it has been show that in some teleosts that the trunk and tail somites form differently during gastrulation. The transition zone between these two regions corresponds, furthermore, to the area of the axial skeleton presenting the highest levels of morphological variability . This might indicate that there are different genetic, cellular, and developmental mechanisms involved in the differential development of the vertebral structures along the vertebral axis, a hypothesis that should be further explored in all vertebrate lineages.
Although not morphologically segmented, the notochord may present a cryptic segmental pattern through spatial and temporal differential gene expression. It is known, for instance, that notochord expression of Shh and Noggin drives the differentiation of the ventral somite into the sclerotome and sclerotome proliferation [34, 35]. Moreover, in fused somite mutants of zebrafish, it has been shown that the sclerotomal polarization is disrupted. The segmentation of the sclerotome-derived neural arches is abnormal although the vertebral centra are correctly specified, which is opposite to the pattern observed in this study. The authors interpret their results as a primordial role of the nothochord in specifying segmental identity and position . The notochord may also represent an ancestrally segmented structure in vertebrates that specified the regular disposition of perichordal rings and, hence, the intersegmental location of centra. Indeed, in some teleosts, the segmental expression of alkaline phosphatase activity (ALP) in the notochord is related to the initial ossification of centra suggesting an active role for the notochord during segmentation . This and related possibilities should be tested in all vertebrate lineages.
The spinal cord may also play an important role in vertebrae differentiation. It has been shown through ablation studies, for instance, that the spinal cord influences the development of the neural arches in the urodeles Ambystoma and Taricha [38–40]; however, the molecular mechanisms involved are unknown at present. Furthermore, the elements of the peripheral nervous system (PNS, neural crest cells and outgrowing motor and sensory neurons) have to migrate out the central nervous system in every segment of the axial skeleton. It has been shown that these elements follow specific movement patterns that are directly related to the anterior/posterior polarization of the somites: they migrate along their anterior parts since they are ‘repulsed’ by molecules at the posterior halves . It has been suggested that in anamniotes, given the scarcity of the sclerotomal cellular population, it is the dermomyotome that drives the repulsion/migration pattern . It remains to be tested then, what are the specific roles of the spinal cord and the paired ganglia present in each segment, if they play any significant function in specifying the intersegmental location of vertebral bodies, and the potential relation between the migrating elements of the PNS, the migrating sclerotomic cells, and the dermomyotome .
Molecular cell-labeling markers for sclerotomal cells that have recently been developed for the axolotl Ambystoma mexicanum  may permit a detailed analysis of the cellular origin of vertebral centra in this amphibian, such that the contribution of each somitic sclerotomal cellular population to each vertebral element could be discerned. Furthermore, cell-labeling experiments of notochord cells would also shed light on the role of the notochord as it is known that notochord cells may contribute to the formation of centra in certain lineages such as in some teleosts  and urodeles [22, 38]; this apparently does not happen in other lineages (e.g., mammals) .
Overall, these proposed lines of research will help determine whether re-segmentation occurs in urodeles and anurans. In addition, they will help to identify the exact cellular origin of centra in amphibians and the tissues and structures involved in vertebral differentiation. More importantly, the study and comparison in an explicit phylogenetic framework of the morphological variations, and their developmental and molecular underpinnings, will provide a better understanding of the homologous and homoplastic elements are responsible for the evolution of the axial skeleton among the particular vertebrates lineages.
Expanding the analytical framework
The axial skeleton is often considered an anatomical module, a morphological unit that defines and characterizes the vertebrate lineage. However, the genetic, developmental, and historical origin of each vertebral element may be different. The different axial components have not evolved at the same geological time , but were only eventually integrated into the functional anatomical module that we observe today. A longstanding debate, for instance, has revolved around the homology of centra in (stem and crown) fossil vertebrates and the modern fishes and tetrapods (e.g., [21, 45, 46]). Most of the comparative studies have approached this question either form a developmental or paleontological perspective, although neither approach has satisfactorily addressed it. Furthermore, accepted views of evolution of axial elements in early tetrapods have been recently challenged by new paleontological findings, which require reinterpreting embryological and developmental evolutionary inferences. For instance, it has been shown that specialization and regionalization of the axial skeleton was already present in rhipidistian fishes, which were though to represent un-regionalized ancestral forms . In the same vein, reverse patterns of ossification in the diplospondylous stem-tetrapod Ichthyostega have been recently reported , which could bring a new perspective concerning the levels of plasticity and developmental axial patterns in tetrapod ancestral forms. Understanding how the different axial components evolved into a genetically, developmentally, ecologically, and evolutionary cohesive structure, therefore, is a major challenge that has to be faced from a multidisciplinary perspective. Evolutionary developmental biology, or evo-devo, would be an appropriate integrative framework for such a study.
Evolutionary developmental biology seeks to explain morphological evolution in a causal context by studying how development generates evolutionary phenotypic variants and how developmental mechanisms evolve over time. Although broad in scope, the bulk of current research in evo-devo is quite specialized and reductionist in its approach, driven mainly by research programs in developmental genetics in model organisms. However, new technical advances have made it more feasible for evo-devo research both in non–model organisms and at the population level. This unusual teratological non-model individual exemplifies the necessity to frame evo-devo research programs at the interface of development, natural history, population variability, and phylogenetics, including the extinct taxa. Much is known about development and evolution of vertebrae but, still, the unusual malformation reported here cannot be explained from a developmental point of view, since the referred mechanisms and developmental processes have been generalized from studies in lineages with different developmental properties and evolutionary histories. Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates. These foundations, however, should not be use to infer common general ‘laws’ for the evolution of the axial skeleton in vertebrates, but to establish the basis for further comparative analyses. Major theoretical contributions of evo-devo would be derived from a comprehensive understanding of the causal links between developmental properties, which includes, but is not restricted to, the genetic and molecular toolkit, and the intraspecific variability of these properties in natural populations, followed by a interspecific (phylogenetic) comparison across a wide range of extinct and extant evolutionary lineages. Therefore, in this “-omics” era, we emphasize an integrative and organismal approach in evolutionary developmental biology as an exceptional tool for the study of morphological diversity and evolution.
We greatly appreciate comments on the manuscript made by A. Machordom, M. García París, and M. Modrell. Comments and suggestions from two anonymous reviewers have also greatly improved the final version of the manuscript. JV was supported by the NKFP project (Faunagenezis 3B-02304) from the National Office for Research and Technology, Hungary, and the Hungarian Scientific Research Fund (OTKA K84071). DB was partially supported by the National Science Foundation EF-0334939 project (USA) and a JAE-DOC fellowship from the CSIC (Spain) under the program “Junta para la Ampliación de Estudios” co-financed by the European Social Fund (ESF). We also acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).
- Geoffroy Saint-Hilaire I: Traité de Tératologie. 1836, Paris: J. B. BaillièreGoogle Scholar
- Alberch P: The logic of monsters: evidence for internal constraints in development and evolution. Geobios. 1989, 12: 21-57.View ArticleGoogle Scholar
- Hawthorne Wilder H: The morphology of cosmobia; speculations concerning the significance of certain types of monsters. Am J Anat. 1908, 8: 355-440. 10.1002/aja.1000080113.View ArticleGoogle Scholar
- Dequéant ML, Pourquié O: Segmental patterning of the vertebrate embryonic axis. Nat Rev Genet. 2008, 9: 370-382.View ArticlePubMedGoogle Scholar
- Hester SD, Belmonte JM, Gens JS, Clendenon SG, Glazier JA: A multi-cell, multi-scale model of vertebrate segmentation and somite formation. PLoS Comput Biol. 2011, 7: e1002155-10.1371/journal.pcbi.1002155.PubMed CentralView ArticlePubMedGoogle Scholar
- Gomez C, Özbudak EM, Wundelich J, Baumann D, Lewis J, Pourquié O: Control of segmented number in vertebrate embryos. Nature. 2008, 454: 335-339. 10.1038/nature07020.View ArticlePubMedGoogle Scholar
- Burke AC, Nelson CE, Morgan BA, Tabin C: Hox genes and the evolution of vertebrate axial morphology. Development. 1995, 121: 333-346.PubMedGoogle Scholar
- Carapuço M, Nóvoa A, Bobola N, Mallo M: Hox genes specify vertebral types in the presomitic mesoderm. Genes Dev. 2005, 19: 2116-2121. 10.1101/gad.338705.PubMed CentralView ArticlePubMedGoogle Scholar
- Wellik M: Hox genes and vertebrate axial pattern. Curr Topics Dev Biol. 2009, 88: 257-278.View ArticleGoogle Scholar
- Liang D, Wu R, Geng J, Wang C, Zhang P: A general scenario of Hox gene inventory variation among major Sarcopterygian lineages. BMC Evol Biol. 2011, 11: 25-10.1186/1471-2148-11-25.PubMed CentralView ArticlePubMedGoogle Scholar
- Cohn MJ, Tickle C: Developmental basis of limblessness and axial patterning in snakes. Nature. 1999, 399: 474-479. 10.1038/20944.View ArticlePubMedGoogle Scholar
- Mansfield JH, Abzhanov A: Hox expression in the American alligator and evolution of archosaurian axial patterning. J Exp Zool. 2010, 314B: 629-644. 10.1002/jez.b.21364.View ArticleGoogle Scholar
- Buchholtz EA, Bailin HG, Laves SA, Yang JT, Chan MY, Drozd LE: Fixed cervical count and the origin of the mammalian diaphragm. Evol & Develop. 2012, 14: 399-411. 10.1111/j.1525-142X.2012.00560.x.View ArticleGoogle Scholar
- Frazzetta TH: Flatfishes, turtles, and bolyerine snakes: evolution by small steps or large, or both?. Evol Biol. 2012, 39: 30-60. 10.1007/s11692-011-9142-7.View ArticleGoogle Scholar
- Johanson Z, Carr R, Ritchie A: Fusion, gene misexpression and homeotic transformation in vertebral development of the gnathostome stem group. Int J Dev Biol. 2010, 54: 71-80. 10.1387/ijdb.072508zj.View ArticlePubMedGoogle Scholar
- Wake DB: The endoskeleton: The comparative anatomy of the vertebral column and ribs. Hyman's Comparative Vertebrate Anatomy. Edited by: Wake MH. 1979, Chicago: University of Chicago Press, 192-237.Google Scholar
- Morin-Kensicki EM, Melancon E, Eisen JS: Segmental relationship between somites and vertebral column in zebrafish. Development. 2002, 129: 3851-3860.PubMedGoogle Scholar
- Nordvik K, Kryvi H, Totland GK, Grotmol S: The salmon vertebral body develops through mineralization of two preformed tissues that are encompassed by two layers of bone. J Anat. 2005, 206: 103-114. 10.1111/j.1469-7580.2005.00372.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Takahashi J, Ohbayashi A, Oginuma M, Saito D, Mochizuki A, Saga Y, Takada S: Analysis of Ripply1/2-deficient mouse embryos reveals a mechanism underlying the rostro-caudal patterning within a somite. Dev Biol. 2010, 342: 134-145. 10.1016/j.ydbio.2010.03.015.View ArticlePubMedGoogle Scholar
- Arratia G: The caudal skeleton of Jurassic teleosts: A phylogenetic analysis. Early Vertebrates and Related Problems in Evolutionary Biology. Edited by: Chang MN, Liu YH, Zhang GR. 1991, Beijing: Science Press, 249-340.Google Scholar
- Wake DB: Aspects of vertebral evolution in the modern Amphibia. Forma et Functio. 1970, 3: 33-60.Google Scholar
- Wake DB, Lawson R: Developmental and adult morphology of the vertebral column in the plethodontid salamander Eurycea bislineata, with comments on vertebral evolution in the Amphibia. J Morphol. 1973, 139: 251-300. 10.1002/jmor.1051390302.View ArticlePubMedGoogle Scholar
- Keller R: The origin and morphogenesis of amphibian somites. Curr Topics Dev Biol. 1999, 47: 183-246.View ArticleGoogle Scholar
- Epperlein HH, Vichev K, Heidrich FM, Kurth T: BMP-4 and Noggin signaling modulate dorsal fin and somite development in the axolotl trunk. Dev Dyn. 2007, 236: 2464-2474. 10.1002/dvdy.21247.View ArticlePubMedGoogle Scholar
- Wake MH, Wake DB: Developmental morphology of early vertebrogenesis in caecilians (Amphibia: Gymnophiona): resegmentation and phylogenesis. Zoology. 2000, 103: 68-88.Google Scholar
- Arntzen JW, Wallis GP: Geographic variation and taxonomy of crested newts (Triturus cristatus superspecies): morphological and mitochondrial DNA data. Contrib Zool. 1999, 68: 181-203.Google Scholar
- Aoyama H, Mizutani-Koseki Y, Koseki H: Three developmental compartments involved in rib formation. Int J Dev Biol. 2005, 49: 325-333. 10.1387/ijdb.041932ha.View ArticlePubMedGoogle Scholar
- Tyl RW, Chernoff N, Rogers JM: Altered axial skeletal development. Birth Def Res. 2007, 2007 (80): 451-472.View ArticleGoogle Scholar
- Kusumi K, Sun ES, Kerrebrock AW, Bronson RT, Chi DC, Bulotsky MS, Spencer JB, Birren BW, Frankel WN, Lander ES: The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nat Genet. 1998, 19: 274-278. 10.1038/961.View ArticlePubMedGoogle Scholar
- Mallo M, Vinagre T, Carapuço M: The road to the vertebral formula. Int J Dev Biol. 2009, 53: 1469-1481. 10.1387/ijdb.072276mm.View ArticlePubMedGoogle Scholar
- Vilhais-Neto GV, Maruhashi M, Smith KT, Vasseur-Cognet M, Peterson AS, Workman JL, Pourquié O: Rere controls retinoic acid signaling and somite bilateral symmetry. Nature. 2010, 463: 953-957. 10.1038/nature08763.View ArticlePubMedGoogle Scholar
- Jockusch EL: Geographic variation and phenotypic plasticity of number of trunk vertebrae in slender salamanders, Batrachoseps (Caudata: Plethodontidae). Evolution. 1997, 51: 1966-1982. 10.2307/2411017.View ArticleGoogle Scholar
- Vaglia JL, White K, Case A: Evolving possibilities: postembryonic axial elongation salamanders with biphasic (Eurycea cirrigea, Eurycea longicauda, Eurycea quadridigitata) and paedomorphic life cycles (Eurycea nana and Ambystoma mexicanum). Acta Zoologica. 2012, 93: 2-13. 10.1111/j.1463-6395.2010.00475.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Fleming A, Keynes RJ, Tannahill D: The role of the notochord in vertebral column formation. J Anat. 2001, 199: 177-180. 10.1046/j.1469-7580.2001.19910177.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang G, Eames BF, Cohn MJ: Evolution of vertebrate cartilage development. Curr Topics Dev Biol. 2009, 86: 16-42.Google Scholar
- Fleming A, Keynes R, Tannahill D: A central role for the notochord in vertebral patterning. Development. 2004, 131: 873-880. 10.1242/dev.00952.View ArticlePubMedGoogle Scholar
- Grotmol S, Nordvik K, Kryvi H, Totland GK: A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies. J Anat. 2005, 206: 427-436. 10.1111/j.1469-7580.2005.00408.x.View ArticlePubMedGoogle Scholar
- Mookerjee HK: On the development of the vertebral column of Urodela. Phil Trans R Soc Lond B. 1930, 218: 415-446. 10.1098/rstb.1930.0010.View ArticleGoogle Scholar
- Hörstadius S: Über die folgen von chorda-exstirpation an späten gastrulae and neurulae von Ambystoma punctatum. Acta Zool. 1944, 25: 1-13. 10.1111/j.1463-6395.1944.tb00342.x.View ArticleGoogle Scholar
- Kitchen JC: The effects of notochordectomy in Ambystoma mexicanum. J Exp Zool. 1949, 112: 393-415. 10.1002/jez.1401120303.View ArticleGoogle Scholar
- Kuan CYK, Tannahill D, Cook GMW, Keynes RJ: Somite polarity and segmental patterning of the peripheral nervous system. Mech Develop. 2004, 121: 1055-1068. 10.1016/j.mod.2004.05.001.View ArticleGoogle Scholar
- Scaal M, Wiegreffe C: Somites compartments in anamniotes. Anat Embryol. 2006, 211: S9-S19.Google Scholar
- Piekarski N, Olsson L: A somitic contribution to the pectoral girdle in the axolotl revealed by long-term fate mapping. Evol & Develop. 2011, 13: 47-57. 10.1111/j.1525-142X.2010.00455.x.View ArticleGoogle Scholar
- Choi KS, Harfe BD: Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs. Proc Natl Acad Sci U S A. 2011, 108: 9484-9489. 10.1073/pnas.1007566108.PubMed CentralView ArticlePubMedGoogle Scholar
- Williams EE: Gadow’s arcualia and the development of tetrapod vertebrae. Quart Rev Biol. 1959, 34: 1-32. 10.1111/j.1469-185X.1959.tb01300.x.View ArticlePubMedGoogle Scholar
- Shishkin MA: The axial skeleton of early amphibians and the origin of resegmentation in tetrapod vertebrae. Trends in Vertebrate Morphology. Edited by: Spletchna H, Hilgers H. 1989, Stuttgart: Gustav Fisher Verlag, 180-195.Google Scholar
- Sallan LC: Tetrapod-like axial regionalization in an early ray-finned fish. Proc R Soc B. 2012, 279: 3264-3271. 10.1098/rspb.2012.0784.PubMed CentralView ArticlePubMedGoogle Scholar
- Pierce SE, Ahlberg PE, Hutchinson JR, Molnar JL, Sanchez S, Tafforeau P, Clack JA: Vertebral architecture in the earliest stem tetrapods. Nature. 2013, 494: 226-230. 10.1038/nature11825.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.