A gene network model accounting for development and evolution of mammalian teeth

Salazar‐Ciudad, Isaac; Jernvall, Jukka

doi:10.1073/pnas.132069499

Cited by 354 publications

(316 citation statements)

References 45 publications

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“…The real complexity of connections between the genes is even more hyperastronomical, and largely unknown, involving, e.g., multiple levels of post-transcriptional regulation (Gerhart and Kirschner, 1997), multiprotein complexes (e.g., Sobott and Robinson, 2002), various forms of second messenger signaling (Hunter, 2000), and purely JTB version 1 3 mechanistical integration of morphogenetic effects of various signaling pathways (Gerhart and Kirschner, 1997;Oster and Murray, 1980;Salazar-Ciudad and Jernvall, 2002). This makes in vivo biological networks effectively unmodelable.…”

Section: Introductionmentioning

confidence: 99%

Simulation study on effects of signaling network structure on the developmental increase in complexity

Keränen

2004

Journal of Theoretical Biology

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The developmental increase in structural complexity in multicellular lifeforms depends on local, often non-periodic differences in gene expression. These depend on a network of gene-gene interactions coded within the organismal genome. To better understand how genomic information generates complex expression patterns, I have modeled the pattern forming behavior of small artificial genomes in virtual blastoderm embryos. I varied several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions, and analyzed their effects on developmental pattern formation. The results show how even simple genomes can generate complex non-periodic patterns under suitable conditions. They also show how the frequency of complex patterns depended on the numbers and relative arrangements of positive and negative interactions. For example, negative co-regulation of signaling pathway components increased the likelihood of (complex) patterns relative to differential negative regulation of the pathway components. Interestingly, neither quantitative differences either in strengths of signaling interactions nor multiple response thresholds to signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique cell types. Thus, with combinatorial code of gene regulation and hierarchical signaling interactions, it is theoretically possible to organize metazoan embryogenesis with just a small fraction of the metazoan genome.Because even small networks can generate complex patterns when they contain a suitable set of connections, evolution of metazoan complexity may have depended more on selection for favourable configurations of signaling interactions than on the increase in numbers of regulatory genes.JTB version 1 2

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Section: Introductionmentioning

confidence: 99%

Simulation study on effects of signaling network structure on the developmental increase in complexity

Keränen

2004

Journal of Theoretical Biology

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“…Although previous computational modeling had implicated lateral growth to control lateral cusp configuration (22), the model used had only a rough depiction of tissue growth dynamics. Therefore, here we used a morphodynamic model incorporating genetic interactions with tissue biomechanics through the ToothMaker interface (12,32).…”

Section: Computational Modeling Implicates Lateral Expansion In Thementioning

confidence: 99%

“…Our specific focus is inspired by early computational modeling, which has implicated that the lateral configuration of cusps depends on lateral expansion of the developing molar (22). Molars typically have lateral cusp configurations that range from largely parallel, as in mice and humans, to alternate, as in the evolutionarily basal mammalian molar, the tribosphenic molar.…”

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confidence: 99%

Mechanical constraint from growing jaw facilitates mammalian dental diversity

Renvoisé

Kavanagh

Lazzari

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Much of the basic information about individual organ development comes from studies using model species. Whereas conservation of gene regulatory networks across higher taxa supports generalizations made from a limited number of species, generality of mechanistic inferences remains to be tested in tissue culture systems. Here, using mammalian tooth explants cultured in isolation, we investigate self-regulation of patterning by comparing developing molars of the mouse, the model species of mammalian research, and the bank vole. A distinct patterning difference between the vole and the mouse molars is the alternate cusp offset present in the vole. Analyses of both species using 3D reconstructions of developing molars and jaws, computational modeling of cusp patterning, and tooth explants cultured with small braces show that correct cusp offset requires constraints on the lateral expansion of the developing tooth. Vole molars cultured without the braces lose their cusp offset, and mouse molars cultured with the braces develop a cusp offset. Our results suggest that cusp offset, which changes frequently in mammalian evolution, is more dependent on the 3D support of the developing jaw than other aspects of tooth shape. This jaw-tooth integration of a specific aspect of the tooth phenotype indicates that organs may outsource specific aspects of their morphology to be regulated by adjacent body parts or organs. Comparative studies of morphologically different species are needed to infer the principles of organogenesis.T he conservation of gene regulatory networks in the development of homologous organs is well exemplified by dentitions. Teeth in fish, reptiles, and mammals have been found to use largely shared developmental gene networks (1, 2). Furthermore, tooth development, similar to organ development in general, results from sequential events that appear to be relatively independent from the development of other organs. In particular, mammalian teeth have been considered highly selfregulatory, as they form inside the dental follicle buffered from the surrounding environment (3-5). The self-regulatory aspect of teeth is further supported by the reiterative use of the same signaling pathways and signaling centers, called enamel knots, present within each growing tooth (2). Experiments on growing teeth have revealed how an activator-inhibitor balance of signaling molecules within a developing tooth and between adjacent teeth regulate dental patterning (6-12).Despite the evidence from mice indicating self-regulation of teeth, several observations suggest an intriguing link between jaw bone and tooth crown formation (3,13,14). In humans, abnormal crown patterns in patients with congenital syphilis have been ascribed to result from infection of the tooth follicle (3). Likewise, loss of function of parathyroid hormone-related protein (PTHrP) leads to loss of alveolar bone resorption and deformation of the tooth crown in the mouse (15)(16)(17)(18)(19). A lethal human syndrome called Blomstrand chondrodysplasia, which invol...

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“…Teeth develop based on the signaling among epithelial and mesenchymal tissues, where the tooth crowns form based on a limited number of epithelial signaling centers called the enamel knots. The model of Salazar-Ciudad and Jernvall (2002) proceeds from prior experimentally generated information about the relations among several molecular components, i.e., genes producing proteins which in turn affect the expression of other genes and their products (Fig. 1A).…”

Section: Mathematical Models Of the Origin Of Morphological Structuresmentioning

confidence: 99%

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

Brigandt

2015

History, Philosophy and Theory of the Life Sciences

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Evolutionary developmental biology (evo-devo) is considered a 'mechanistic science,' in that it causally explains morphological evolution in terms of changes in developmental mechanisms. Evo-devo is also an interdisciplinary and integrative approach, as its explanations use contributions from many fields and pertain to different levels of organismal organization. Philosophical accounts of mechanistic explanation are currently highly prominent, and have been particularly able to capture the integrative nature of multifield and multilevel explanations. However, I argue that evo-devo demonstrates the need for a broadened philosophical conception of mechanisms and mechanistic explanation.Mechanistic explanation (in terms of the qualitative interactions of the structural parts of a whole) has been developed as an alternative to the traditional idea of explanation as derivation from laws or quantitative principles. Against the picture promoted by Carl Craver, that mathematical models describe but usually do not explain, my discussion of cases from the strand of evo-devo which is concerned with developmental processes points to qualitative phenomena where quantitative mathematical models are an indispensable part of the explanation. While philosophical accounts have focused on the actual organization and operation of mechanisms, properties of developmental mechanisms that are about how a mechanism reacts to modifications are of major evolutionary significance, including robustness, phenotypic plasticity, and modularity. A philosophical conception of mechanisms is needed that takes into account quantitative changes, transient entities and the generation of novel types of entities, feedback loops and complex interaction networks, emergent properties, and, in particular, functional-dynamical aspects of mechanisms, including functional (as opposed to structural) organization and distributed, system-wide phenomena. I conclude with general remarks on philosophical accounts of explanation.

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A gene network model accounting for development and evolution of mammalian teeth

Cited by 354 publications

References 45 publications

Simulation study on effects of signaling network structure on the developmental increase in complexity

Simulation study on effects of signaling network structure on the developmental increase in complexity

Mechanical constraint from growing jaw facilitates mammalian dental diversity

Evolutionary Developmental Biology and the Limits of Philosophical Accounts of Mechanistic Explanation

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