Research themes

• Does the modular structure of GRNs influence shape evolution?

• Finding new rules for the evolution of repeated structures

• Genomic and developmental basis of sensory adaptations

• Evo-devo of the Eda pathway: from the evolution of signaling to the establishment of shape

How the modular structure of developmental networks facilitate variation?

One long-standing question in evolutionary biology is why some phenotypes are frequently realized while other theoretically possible ones seemingly never are? This paradox has commonly been hypothesized to be caused by biases or constraints on developmental processes that result in the production of a limited number of phenotypes along certain ontogenetic path of least resistance. Among these potential biases, the modular organization of developmental networks, as theorized by Eric Davidson has shown particular promise. This theory suggests that Gene Regulatory Networks (GRNs) that control organ formation have core modules comprised of conserved circuits of genes, and sub-modules of downstream, secondary circuits of genes that are more susceptible to variation. While some of these modules have been identified, for example in Darwin finches beak or in the sea urchin, we still have a limited understanding of how the organization of GRNs influence the evolution of phenotypes, mainly because only a comparative approach on a large number of species can identify the features of GRNs needed to achieve essential phenotypic outcomes and which one are free to change during evolution. To solve this problem, the evo-devo field needs new ecologically and morphologically diverse model systems for which the development is accessible in a large number of species at the genomic, developmental and phenotypic level. In my research program, I use the incredible variation of the Noctilionoid bats and their teeth as a model system to study how the structural organization of GRNs both constrains and facilitates the evolution of shape and new organs.

My primary research goals are to: 1) functionally link shifts in gene expression in the bat first molar to differences in morphology among closely related species to identify core and sub-modules of the tooth GRN, and 2) use these data to test how the modular structure of developmental GRNs bias and/or facilitate the evolution of new phenotypes, using multi-integrative approaches. This project is currently funded by a NSF IOS (awarded in July 2020) that I conceived and wrote to support my independent research in collaboration with my PI Karen Sears (UCLA), Sharlene Santana (UW) and Paul François (McGill).


Bat teeth

Developmental rules behind repeated structure evolution: bat teeth as a model system

To pursue my work on the implication of developmental mechanisms in generating morphological variation, I have developed an independent axis of research that constitutes the foundation of my future lab. Using the incredible variation in bat tooth number, size and shape, I investigated the existence of developmental rules that control the evolution of repeated structures both in term of type/class (premolar, molar) and morphology. Combining morphometric and quantitative data from 117 adult species representative of this diversity, I showed for the first time that different tooth class are generated by independent cascades that differ in their dynamic. To confirm this result and find new rules to explain this observation, I investigated the development of 12 different bat species across 8 different developmental stages using µCTs scans, gene expression and cell division data, as well as mathematical modeling. These results reveal that growth, by perturbing Turing patterns, is sufficient to produce the variation of tooth number and size seen in Noctilionoids and established growth as a new rule for serial organ evolution. The paper about these results is currently being written and opens new questions that I plan to study in my new lab regarding the fine interplay between Turing pattern and growth to produce variation.

The evolution of sensory systems in Noctilionoid bats

The ecological theory of adaptive radiation remains the single theoretical framework to explain the taxonomic and functional diversity of all organisms in the biosphere. The driving force at the center of this theory is ecological opportunity, a set of resources or adaptive zone that becomes available to a taxonomic group through the evolution of a key innovation, colonization of new environment, or the extinction of competitors. Key innovations, novel phenotypic traits that promote diversification, often involve sensory adaptations that enable access to hitherto unavailable ecological resources. Where they emerge, these sensory adaptations confer such dramatic advantages that they raise an enduring question: why don’t species evolve multiple sensory adaptations simultaneously?

To elucidate the genomic and developmental mechanisms underlying sensory adaptations we focused on noctilionoid bats —an exceptionally diverse and ecologically important clade of mammals. In a collaboration involving four labs, we propose will uncover the genomic and functional morphological basis of variation in four sensory systems: hearing by targeting the cochlea, vision via photoreceptor cells and relative eye size, olfaction by studying the olfactory epithelium and olfactory bulb, and chemosensation by analyzing the vomeronasal organ and accessory olfactory bulb.

I specifically studied the evolution of vision (see Sadier et al. 2018 ) in Noctilionoid bats, showing that vision plays un important role in bat ecology and that the evolution of color vision is bats if highly mosaic and involve multiple processes at different levels of regulation. Our future research regarding that project is to investigate the developmental mechanisms at the origin of this rapid evolution of color vision by combining classical developmental approaches, RNAseq and modeling. In parallel, I am leading a study on the evolution of hearing and echolocation in the same group of bats to investigate the evolution of echolocation in relation with ecological parameters in this group. Ultimately, these projects will highlight the evolution of sensory systems as a whole, and lead us to conclude about the existence of possible trade-off between sensory systems in mammals.



EDA pathway

During my PhD, I worked on the evo-devo of the Eda Pathway, a signaling pathway which is implicated in the development of ectodermal appendages (such as hair, tooth, nails, scales, feather etc) and which has been shown to be involved in adaptive evolution in vertebrates (see our review in my CV, Sadier et al. TIG). My project was divided in two parts that focused on different aspects of the evolution of this pathway.



In my PhD work, I investigated the role of the ectodysplasin (EDA) pathway in the evolution and development of ectodermal appendages (including teeth, nail, hair, external glands) in mammals from a molecular and developmental point of view. This pathway is of particular interest as many examples have revealed how it has been modified during evolution to produce variation. In my current research (see above), the EDA pathways is still a pathway of interest given its role in the development of ectodermal appendages and their evolution.

Edar as a regulator of tooth patterning

To get insight in to the role of this pathway in organ initiation and morphogenesis, I studied the role of the receptor EDAR in the sequential patterning of molars in mice. In the last two decades, this gene (as well as the other members of the pathway) has been shown to play an important role tooth morphogenesis. Combining in situ hybridization (ISH), in vitro molar culture, and fine mathematical modeling in wild-type and mutant mice, I used the dynamic of expression of EDAR to explain how tooth signaling center form sequentially. Our study revealed that, contrarily to what was previously thought, a newly formed tooth organizing center can actively impair or erase a previously formed one, likely reflecting the evolutionary history of mice, who lost premolars while maintaining their embryonic organizing centers. As a result, this study not only explained the complex patterning at the origin of tooth development but also uncover how patterning can be used by evolution to produce variation.

More broadly, we showed that overwriting or correcting previously established patterns during development might be more common than anticipated, simply due to the fact that developmental programs are modified by incrementation during evolution. This work has been published in Plos Biology

Evolution by tinkering of gene isoforms: the case of Edaradd implicated in skin appendage development

My first project was based on the observation that the adaptor of this pathway, EDARADD, exhibits some interesting variations in the conservation of its isoforms that could potentially lead to morphological variation. To explore this idea, I investigated the conservation of these isoforms in mammals combining the use of databases and cloning and showed that one of the two mammalian isoforms exhibits secondary losses in various mammals. Then, I used functional approaches to show that the two isoforms possess a different activity, leading to a fine modulation of the pathway with different morphological outcomes.

This work was one of the first example to highlight the importance of gain/loss of isoforms in modifying the activity of developmental pathways (BMC EcoEvo) and highlighted a new implication of the EDA pathway in morphological evolution.