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  • 1
    Publication Date: 2010-03-12
    Description: The relationship between the genotype and the phenotype, or the genotype-phenotype map, is generally approached with the tools of multivariate quantitative genetics and morphometrics. Whereas studies of development and mathematical models of development may offer new insights into the genotype-phenotype map, the challenge is to make them useful at the level of microevolution. Here we report a computational model of mammalian tooth development that combines parameters of genetic and cellular interactions to produce a three-dimensional tooth from a simple tooth primordia. We systematically tinkered with each of the model parameters to generate phenotypic variation and used geometric morphometric analyses to identify, or developmentally ordinate, parameters best explaining population-level variation of real teeth. To model the full range of developmentally possible morphologies, we used a population sample of ringed seals (Phoca hispida ladogensis). Seal dentitions show a high degree of variation, typically linked to the lack of exact occlusion. Our model suggests that despite the complexity of development and teeth, there may be a simple basis for dental variation. Changes in single parameters regulating signalling during cusp development may explain shape variation among individuals, whereas a parameter regulating epithelial growth may explain serial, tooth-to-tooth variation along the jaw. Our study provides a step towards integrating the genotype, development and the phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salazar-Ciudad, Isaac -- Jernvall, Jukka -- England -- Nature. 2010 Mar 25;464(7288):583-6. doi: 10.1038/nature08838. Epub 2010 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departament de Genetica i Microbiologia, Facultat de Biociencies, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. isaac.salazar@uab.cat〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220757" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Regulatory Networks/genetics ; Genotype ; *Models, Biological ; Phenotype ; *Phoca/anatomy & histology/genetics/growth & development ; Signal Transduction ; Tooth/*anatomy & histology/growth & development/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-08-01
    Description: The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological characters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the developmental underpinnings of character inter-dependence remain obscure because experiments frequently do not provide detailed resolution of morphological characters. Here we show experimentally and computationally how gradual modification of development differentially affects characters in the mouse dentition. We found that intermediate phenotypes could be produced by gradually adding ectodysplasin A (EDA) protein in culture to tooth explants carrying a null mutation in the tooth-patterning gene Eda. By identifying development-based character inter-dependencies, we show how to predict morphological patterns of teeth among mammalian species. Finally, in vivo inhibition of sonic hedgehog signalling in Eda null teeth enabled us to reproduce characters deep in the rodent ancestry. Taken together, evolutionarily informative transitions can be experimentally reproduced, thereby providing development-based expectations for character-state transitions used in evolutionary studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252015/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harjunmaa, Enni -- Seidel, Kerstin -- Hakkinen, Teemu -- Renvoise, Elodie -- Corfe, Ian J -- Kallonen, Aki -- Zhang, Zhao-Qun -- Evans, Alistair R -- Mikkola, Marja L -- Salazar-Ciudad, Isaac -- Klein, Ophir D -- Jernvall, Jukka -- DP2 OD007191/OD/NIH HHS/ -- DP2-OD007191/OD/NIH HHS/ -- K99 DE024214/DE/NIDCR NIH HHS/ -- R01 DE021420/DE/NIDCR NIH HHS/ -- R01-DE021420/DE/NIDCR NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):44-8. doi: 10.1038/nature13613. Epub 2014 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. ; 1] Program in Craniofacial and Mesenchymal Biology, University of California, San Francisco, San Francisco, California 94114, USA [2] Department of Orofacial Sciences, University of California, San Francisco, San Francisco, California 94114, USA. ; Division of Materials Physics, Department of Physics, University of Helsinki, P.O. Box 64, FIN-00014 Helsinki, Finland. ; Key Laboratory of Evolutionary Systematics of Vertebrates, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China. ; 1] School of Biological Sciences, Monash University, Victoria 3800, Australia [2] Geosciences, Museum Victoria, GPO Box 666, Melbourne, Victoria 3001, Australia. ; 1] Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland [2] Genomics, Bioinformatics and Evolution Group. Department de Genetica i Microbiologia, Universitat Autonoma de Barcelona, Cerdanyola del Valles 08193, Spain. ; 1] Program in Craniofacial and Mesenchymal Biology, University of California, San Francisco, San Francisco, California 94114, USA [2] Department of Orofacial Sciences, University of California, San Francisco, San Francisco, California 94114, USA [3] Department of Pediatrics, University of California, San Francisco, San Francisco, California 94114, USA [4] Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079326" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Computer Simulation ; Ectodysplasins/deficiency/genetics/pharmacology ; Female ; *Fossils ; Gene Deletion ; Hedgehog Proteins/antagonists & inhibitors/genetics ; In Vitro Techniques ; Male ; Mice ; Molar/anatomy & histology/drug effects/growth & development ; Phenotype ; Signal Transduction/drug effects ; Tooth/*anatomy & histology/drug effects/*growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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