Team

DEMO

Modeling olfactory organ development

Team manager: Batut Julie

Presentation

One of the greatest scientific challenges in developmental biology is to discover the mechanisms that coordinate the processes of cell identity and properties in order to understand how cells interact with each other to ultimately generate a functional organ. We aim to understand how organs are formed using theoretical modelling, live imaging and bioinformatics approaches. In particular, we are interested in the development of the olfactory organ in zebrafish, which comprises two waves of early neurogenesis: progenitors and mature olfactory sensory neurons (OSN) whose morphometric characteristics are well described. The project aims to characterize the establishment of progenitor cells, their evolution during development and their link with the mature OSNs.

Project 1

Modularity refers to a model of connectivity in which elements are grouped into strongly connected sub-assemblies, called modules or building blocks. This is an important property in biology, as it allows a system to ‘maintain its current state’ while allowing for further evolution. The properties attributed to modules are discrete organization defined by the expression of specific genes and occupation of specific physical territories. In vertebrates, the functional and architectural organization of the olfactory system is conserved throughout evolution. The olfactory organ is composed of different types of olfactory sensory neurons, the OSNs, each capable of detecting specific odorous molecules, organized with a specific shape and position, and each expressing a set of specific genes. However, the progenitor cell population has not yet been characterized. Our aim is to break down the formation of the olfactory sensory organ into modules: a genetic module and a morphometric and behavioral module. We are therefore developing multidisciplinary approaches that use a combination of qualitative and quantitative imaging on the zebrafish embryo, data science, machine learning and image analysis and mathematical models to identify the two modules and assemble them in order to generate a single-cell transcriptomic atlas, dynamically linked to cellular behaviors and capable of predicting the architecture of a complex biological system: in this case, the olfactory sensory organ.

Project 2

The accessibility and relative simplicity of the olfactory organ in the zebrafish embryo makes it a model of choice for studying morphogenesis processes. The precursors of the olfactory placodes (pioneer neurons or EON) are located as early as 12 hours post fertilization (hpf) at the edge of the neural plate and form a horseshoe around the telencephalon. Then, an active convergence movement assembles the olfactory placode, which forms two spherical groups on either side of the telencephalon between 18 and 21 hpf. In order to study these movements in greater depth, we want to develop an intermediate model between the embryo and our mathematical models, enabling us to recreate the morphogenesis of the olfactory organ on a 3D printed chip, the OlfactoChip. This project is built on our collaboration with LAAS-CNRS. The multiplexing of our samples will enable us to use a high-throughput quantitative and qualitative approach to characterize the migratory behavior of our olfactory cells.

Team members

– Foncy, J., Kwapisz, M., Knibiehler, M & Batut, J.
 Collectively building a mentor–mentee relationship through a one-day workshop 
Nature Biotechnology 2023 Dec

– Marie Zilliox, Vanessa Tillement, Thomas Mangeat, Sophie Polès, Patrick Blader and Julie Batut.
 Protocol to locally express cxcl12a during zebrafish olfactory organ development by combining IR-LEGO with live imagingStar Protocols 2023 Aug

– Julie Batut, Marina Kvaskoff & May C. Morris . 
When mentoring matters: a French mentoring program for women in science Nature Biotechnology
 2021 Jun Batut, J., Kvaskoff, M. & Morris, M.C. When mentoring matters: a French mentoring program for women in science. Nat Biotechnol 39, 776–779 (2021). https://doi.org/10.1038/s41587-021-00951-2

– Raphaël Aguillon, Romain Madelaine, Marion Aguirrebengoa, Harendra Guturu, Sandra Link, Pascale Dufourcq, Virginie Lecaudey, Gill Bejerano, Patrick Blader, Julie Batut.
 Morphogenesis is transcriptionally coupled to neurogenesis during peripheral olfactory organ development
 Development 2020 Nov

Funding

Affiliation