Biology subjects

Pantalacci, S.

Publications and source records attributed to Pantalacci, S..

6 recordsLinked to original sources

bioRxiv2026

Patterns of molecular conservation along tooth development are only partly shaped by evolutionary pressures on tooth

Although it is well established that certain stages of development are molecularly more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that the cause of conservation of expression and of coding sequences changes over molar development. Gene expression levels display a classical increase of divergence as development progresses. In terms of genes expressed, the composition of early and late stages is better conserved and enriched in pleiotropic genes, yet each stage mobilizes different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. Moreover similar patterns of higher divergence of gene sets and of coding sequences at mid development, are caused by different biological phenomena, in that case heterochronies and blood colonisation respectively. In conclusion, the patterns of molecular conservation in developing molars are shaped by a combination of processes intrinsic to the teeth, and by negative and positive selection on functions which are mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems. AUTHOR SUMMARYFor species to evolve different adaptations to different life styles, their anatomy has to evolve correspondingly. This in turn implies evolution of the embryonic development of anatomical structures. Notably, tooth shape can evolve rapidly as an adaptation to different diets. Mice and hamsters are closely related rodents who yet differ in the shape of their molars, and thus in their development. In this study, we investigated why the genes active in molar development are more or less similar between the two species from early tooth bud to fully formed embryo molar. We found that early and late molar development were slow evolving, while mid-development was evolving faster. But surprisingly, this was in part due not to tooth evolution, but to the involvement of genes which are active in other processes in the body. For example an influx of immune cells also brings fast evolving immune genes. This helps us understand better the complexity of causes of apparently simple evolutionary patterns.

evolutionary biology↗

bioRxiv2025

Pleiotropy accelerates tooth phenotypic and genomic evolution - An in silico study under the lens of development

Pleiotropy, which can occur when a gene affects multiple traits, is a central property of living organisms, influencing their response to mutations and their evolutionary trajectories. Despite many studies and discussions, it remains very difficult to reconcile molecular, developmental and quantitative evolutionary genetics viewpoints on pleiotropy and appreciate how much it puts constraints on genetic evolution, phenotypic evolution and adaptation. Here, we revisit this question by simulating evolution in silico. Our model captures multiple levels of integration observed in complex organisms: from genes to development to phenotype to fitness, additionally allowing to remove pleiotropy to directly test its effect. We focus on the pleiotropic interactions between two organs, specifically teeth. Fitness is determined from the functional interaction between these two teeth, which are produced by an in silico model of tooth morphogenesis. The developmental parameters are produced by a genome consisting of pleiotropic genes which may be influenced by one tooth-specific transcriptional regulator per tooth. Our simulations with and without pleiotropy confirm several acknowledged consequences of pleiotropy. It reduced genetic and phenotypic exploration, and facilitated the rapid accumulation of adaptive mutations in the modular cis-regulatory regions of pleiotropic genes, which are specific to each tooth. Unexpectedly, pleiotropy promoted fitness improvements, morphological complexity, and the accumulation of genetic divergence. Mutations in pleiotropic genes contributed significantly to adaptation, and removing pleiotropy did not increase the proportion of adaptive mutations. Thus pleiotropy does not act as a conservative force, but a channeling force promoting genetic divergence. Significance StatementThe notion of "Gene pleiotropy", just as the notion of "gene", crosses different fields of biology, but appreciations vary on how frequent it is and how much it favors conservation or divergence at the molecular, developmental or phenotypic scale. One reason is the discrepancies of viewpoints between these three scales, another the difficulty to manipulate pleiotropy experimentally. Here, we performed in silico evolution experiments with a computational toy model focusing on the pleiotropy between two organs while bridging the molecular, developmental and phenotypic scales. Moreover, we compared evolutionary scenarios where the two organs shared or not pleiotropic genes. Our results reconcile observations and show that sharing pleiotropic genes accelerates genetic divergence, even though non-pleiotropic genes diverge faster than pleiotropic genes.

evolutionary biology↗

bioRxiv2025

Inverse hourglass pattern of conservation in rodent molar development.

Although it is well established that certain stages of development are more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that molar development is characterized by a rarely observed pattern of conservation of expression level and coding sequences forming an inverse hourglass, with more conservation at the beginning and end of morphogenesis than at intermediate stages. As the development of the rodent molar is well described, we were able to link this pattern to the properties of the expressed genes and the activity of different developmental processes. Early and late stages mobilize different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. The particularities of dental morphogenesis and homeostasis, with the degradation of certain tissues at the end of development and the hosting of immune cells, as well as heterochronies linked to adaptations, also probably contribute to the pattern. Our study of the different actors explains the inverted hourglass of molars by a combination of processes intrinsic to the teeth, and by negative and positive selection which is mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems.

evolutionary biology↗

bioRxiv2024

Convergent transcriptomic and genomic adaptation in xeric rodents

Repeated adaptations rely in part on convergent genetic changes. The extent of convergent changes at the genomic scale is debated and may depend on the interplay between different factors. Rodents have repeatedly adapted to life in arid conditions, notably with altered renal morphology and physiology. This occurred at different time periods, allowing us to test the importance of time in convergent genomic evolution. We analyzed kidney transcriptomes from 34 species to quantify and characterize convergent evolution at the level of gene expression, tissue composition, and coding sequences. We found that several genes showed convergent expression changes, some of which also carried convergent changes in their coding sequence. We then subdivided these data to test the influence of evolutionary history. First, within the subfamily Murinae, we found more convergent gene expression, reflecting convergent changes in cell proportions. Second, we compared data for recent (within genera) and ancient (between genera) adaptations, and observed more convergent changes in the latter. Our study shows that adaptation to xeric environments in rodents involves repeated changes in tissue composition, gene expression and coding sequences, and that the degree of convergent evolution increases with both the age of the adaptations and species relatedness.

evolutionary biology↗

bioRxiv2020

Comparison of developmental genome expression in rodent molars reveals extensive developmental system drift.

Serial appendages are similar organs found at different places in the body, such as fore/hindlimbs or different teeth. They are bound to develop with the same pleiotropic genes, apart from identity genes. These identity genes have logically been implicated in cases where a single appendage evolved a drastically new shape while the other retained an ancestral shape, by enabling developmental changes specifically in one organ. Here, we showed that independent evolution involved developmental changes happening in both organs, in two well characterized model systems. Mouse upper molars evolved a new dental plan with two more cusps on the lingual side, while the lower molar kept a much more ancestral morphology, as did the molars of hamster, our control species. We obtained quantitative timelines of cusp formation and corresponding transcriptomic timeseries in the 4 molars. We found that a molecular and morphogenetic identity of lower and upper molars predated the mouse and hamster divergence and likely facilitated the independent evolution of molars lingual side in the mouse lineage. We found 3 morphogenetic changes which could combine to cause the supplementary cusps in the upper molar and a candidate gene, Bmper. Unexpectedly given its milder morphological divergence, we observed extensive changes in mouse lower molar development. Its transcriptomic profiles diverged as much as, and co-evolved extensively with, those of the upper molar. Consistent with the transcriptomic quantifications, two out of the three morphogenetic changes also impacted lower molar development. Moving to limbs, we show the drastic evolution of the bat wing also involved gene expression co-evolution and a combination of specific and pleiotropic changes. Independent morphological innovation in one organ therefore involves concerted developmental evolution of the other organ. This is facilitated by evolutionary flexibility of its development, a phenomenon known as Developmental System Drift. AUTHOR SUMMARYSerial organs, such as the different wings of an insect or the different limbs or teeth of a vertebrate, can develop into drastically different shapes due to the position-specific expression of so-called "identity" genes. Often during evolution, one organ evolves a new shape while another retains a conserved shape. It was thought that identity genes were responsible for these cases of independent evolution, by enabling developmental changes specifically in one organ. Here, we showed that developmental changes evolved in both organs to enable the independent evolution of the upper molar in mice and the wing in bats. In the organ with the new shape, several developmental changes combine. In the organ with the conserved shape, part of these developmental changes are seen as well. This modifies the development but is not sufficient to drastically change the phenotype, a phenomenon known as "Developmental System Drift", DSD. Thus, the independent evolution of one organ relies on concerted molecular changes, which will contribute to adaptation in one organ and be no more than DSD in another organ. This concerted evolution could apply more generally to very different body parts and explain previous observations on gene expression evolution.

evolutionary biology↗

bioRxiv2018

Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning

The generation of patterns during development is generally viewed as a direct process. In the mouse jaw, however, the sequential patterning of molars initiates with abortive tooth signaling centers called MS and R2, thought to be vestiges of the lost rodent premolars. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that Edar expression reveals the hidden dynamics of signalling centers patterning. First, Edar expression evidenced a hidden two-step patterning process that we modelled with a single activator-inhibitor pair: the epithelium is initially broadly activated, then activation becomes restricted in space to give rise to the signalling centers. Second, Edar expression unveils successive phases of pattern making and pattern erasing events, a phenomenon that we called a developmental palimpsest. MS is erased by a broad activation for the benefit of R2, which itself is erased before it recovers when the first molar signaling center forms. In the lower but not the upper jaw, the two neighboring signaling centers then fuse into a single elongated center. Our model recapitulated the erasure of the R2 signaling center by the wave of activation that precedes the formation of M1 signaling center, and predicted the surprising rescue of R2 in the context of an Edar mutant with reduced activation. It suggested that R2 was not intrinsically defective, but actively outcompeted by M1 formation. We confirmed this by cultivating R2 separately from the posterior tissue and showing it could then generate a tooth. Finally, by introducing chemotaxis as a secondary process of tooth germ maturation, we recapitulated the fusion of R2 and M1 in the lower jaw only, and the loss of fusion when Edar function is impaired in organ cultures. In conclusion, we have uncovered a highly indirect and dynamic nature of pattern formation in the molar field that could nevertheless be simulated with simple mathematical models. Our study argues for viewing embryonic patterns as dynamical objects rather than as fixed endpoints, where dynamics is essential to the outcome of the patterning process.

developmental biology↗