The evolutionary relationships of extinct species are ascertained primarily through the analysis ... more The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological char- acters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the develop- mental 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 modi- fication 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 infor- mative transitions can be experimentally reproduced, thereby providing development-based expectations for character- state transitions used in evolutionary studies.
Proceedings of the National Academy of Sciences of the United States of America, Jan 5, 2006
The single replacement from milk teeth to permanent teeth makes mammalian teeth different from te... more The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized beta-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of beta-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more c...
The evolutionary relationships of extinct species are ascertained primarily through the analysis ... more 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.
The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan,... more The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan, and the morphological plasticity of the shell has promoted the adaptive radiation of turtles. The shell, comprising a dorsal carapace and a ventral plastron, is a layered structure formed by basal endochondral axial skeletal elements (ribs, vertebrae) and plates of bone, which are overlain by keratinous ectodermal scutes. Studies of turtle development have mostly focused on the bones of the shell; however, the genetic regulation of the epidermal scutes has not been investigated. Here, we show that scutes develop from an array of patterned placodes and that these placodes are absent from a soft-shelled turtle in which scutes were lost secondarily. Experimentally inhibiting Shh, Bmp or Fgf signaling results in the disruption of the placodal pattern. Finally, a computational model is used to show how two coupled reaction-diffusion systems reproduce both natural and abnormal variation in tu...
One of the main aims of developmental biology is to understand how a single and apparently homoge... more One of the main aims of developmental biology is to understand how a single and apparently homogeneous egg cell achieves the intricate complexity of the adult. Here we present two models to explain the generation of developmental patterns through interactions at the gene level. One model considers direct-contact induction between cells while the other takes into account diffusion of hormones. We show that sets of cells involving identical gene networks and communicating through hormones spontaneously exhibit ordered patterns. We have characterized these patterns and the specific networks responsible for them. The models allow to (i) compare diffusion and direct-contact induction processes as mechanisms of pattern generation; (ii) identify the possible range of behaviour of real gene networks and (iii) suggest causal mechanisms to generate known patterns. The evolutionary implications are discussed.
The evolutionary relationships of extinct species are ascertained primarily through the analysis ... more The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological char- acters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the develop- mental 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 modi- fication 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 infor- mative transitions can be experimentally reproduced, thereby providing development-based expectations for character- state transitions used in evolutionary studies.
Proceedings of the National Academy of Sciences of the United States of America, Jan 5, 2006
The single replacement from milk teeth to permanent teeth makes mammalian teeth different from te... more The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized beta-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of beta-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more c...
The evolutionary relationships of extinct species are ascertained primarily through the analysis ... more 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.
The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan,... more The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan, and the morphological plasticity of the shell has promoted the adaptive radiation of turtles. The shell, comprising a dorsal carapace and a ventral plastron, is a layered structure formed by basal endochondral axial skeletal elements (ribs, vertebrae) and plates of bone, which are overlain by keratinous ectodermal scutes. Studies of turtle development have mostly focused on the bones of the shell; however, the genetic regulation of the epidermal scutes has not been investigated. Here, we show that scutes develop from an array of patterned placodes and that these placodes are absent from a soft-shelled turtle in which scutes were lost secondarily. Experimentally inhibiting Shh, Bmp or Fgf signaling results in the disruption of the placodal pattern. Finally, a computational model is used to show how two coupled reaction-diffusion systems reproduce both natural and abnormal variation in tu...
One of the main aims of developmental biology is to understand how a single and apparently homoge... more One of the main aims of developmental biology is to understand how a single and apparently homogeneous egg cell achieves the intricate complexity of the adult. Here we present two models to explain the generation of developmental patterns through interactions at the gene level. One model considers direct-contact induction between cells while the other takes into account diffusion of hormones. We show that sets of cells involving identical gene networks and communicating through hormones spontaneously exhibit ordered patterns. We have characterized these patterns and the specific networks responsible for them. The models allow to (i) compare diffusion and direct-contact induction processes as mechanisms of pattern generation; (ii) identify the possible range of behaviour of real gene networks and (iii) suggest causal mechanisms to generate known patterns. The evolutionary implications are discussed.
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Papers by Isaac Salazar-ciudad