PhD thesis in vertebrate evo-devo: mechanisms of asymmetry formation in the river lamprey epithalamus (M/F)

Job Description

Thesis Subject

A remarkable characteristic of the epithalamus is that in many vertebrates, it exhibits asymmetries between its left and its right sides. Comparative analyses across vertebrates, including osteichthyans, chondrichthyans and cyclostomes, suggest that despite a considerable variability in their degree and nature, these asymmetries share an ancient origin in the taxon. How underlying developmental mechanisms vary to account for both their unity and diversifications remains poorly understood. Analyses in the zebrafish and a cartilaginous fish, the small spotted catshark, suggest that in ancestral vertebrates, the Wnt signaling pathway was employed several times in the formation of epithalamic asymmetries: in several distinct territories, with different cellular functions and under different regulatory modalities. In this scenario, differential retentions of these Wnt roles depending on taxa could account for the variations in epithalamic asymmetry patterns observed across vertebrates. The project aims at testing this hypothesis, focusing on a cyclostome, the river lamprey. More specifically, its major objectives are:
- to decipher the molecular and cellular mechanisms of epithalamic asymmetry formation in the river lamprey, with a focus on Wnt signaling
- to compare these mechanisms with those employed in epithalamic asymmetry formation in the zebrafish and in the catshark, in order to infer the vertebrate ancestral state.

The experimental strategy will rely on three complementary approaches:
1. a reconstruction of cellular transcriptomic trajectories and of their asymmetries in the river lamprey developing epithalamus and a comparison of the results to those obtained in the catshark: technique, snRNA-seq (SPLIT-seq)
2. the characterization of the spatial distribution of successive states of neural progenitors and neuronal precursors of the major epithalamic territories, and an analysis of expression profiles of candidate components and regulators of the Wnt pathway: techniques, Stereo-seq, ISH (in situ hybridization), HCR (hybridization chain reaction)-ISH
3. a characterizarion of the cellular and molecular roles of Wnt signaling, using functional analyses of components and regulators of the pathway: techniques, pharmacological treatments, gene edition using the CRISPR-cas9 system.

References:
Guichard et al. 2025. The lamprey habenula provides an extreme example for the temporal regulation of asymmetric development. Front. Cell Dev. Biol. 13:1528797.
Lanoizelet et al. 2024. Analysis of a shark reveals ancient, Wnt-dependent, habenular asymmetries in vertebrates. Nature Commun., 15:10194.
Michel et al. 2022. Diversification of habenular organization and asymmetries in teleosts: Insights from the Atlantic salmon and European eel. Front. Cell. Dev. Biol. 10:1015074..
Lagadec et al. 2018. Neurogenetic asymmetries in the catshark developing habenulae: mechanistic and evolutionary implications. Sci. Rep. 8(1):4616. doi: 10.1038/s41598-018-22851-3.

Your Work Environment

The doctoral student will be hosted in UMR7232, Integrative Biology of Marine Organisms, under the supervision of Sylvie Mazan. He/she will benefit from the support of an engineer in bioinformatics and a CNRS research engineer with a strong expertise of all techniques employed in the project. He/she will have an access to all the technological platforms of the Banyuls Oceanological Observatory required for the project (aquariology, molecular biology, imaging). He/she will interact with the national and international collaborators of the team.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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