Retinogenesis group

Research interests

Our group is interested in the development of the nervous system, and uses the retina as a model. The retina is indeed a model system for neurobiologists, essentially because of its laminated structure with a limited number of neuron types and its accessibility. We are working on Xenopus retina. Xenopus offers many advantages for in vivo embryology approaches (egg production on demand, embryos develop very rapidly in a petri dish, up to thousands embryos per female, which are of an optimal size for manipulations, possibility of microinjections, transplantations, transgenesis). Our work aims at understanding the molecular mechanisms controling retinal cell proliferation, specification and differentiation.

Retinal cell fate determination

Retinal precursor cells give rise to both the neural retina and the retinal pigment epithelium. The neural retina itself contains five major types of neurons and one type of glial cells. Retinal precursors are multipotent, they can give rise to all these cell types. We are interested in understanding how these different cell types are established. We are currently focussing our work on transcription factors potentially involved in neural versus glial fate determination.

Post-transcriptionnal gene regulation during retinogenesis

RNA binding protein (RBP) control multiple steps of nuclear and cytoplasmic RNA processing including alternative splicing, stabilization, transport and translational repression of RNAs. Very little is known on the role of these RBP during development. Some RBPs have been shown to be expressed in the developing nervous system, such as ELAV/Hu, FMRP, Nova, ZBP, CPEB, Musashi, Staufen or QKI. We got interested in such RNA binding proteins in Xenopus, using the retina as a model to understand their function in the nervous system development. For example, we studied a novel RNA binding protein, Xseb4R. This study allowed us to position for the first time a post-transcriptional factor in the genetic cascade of retinogenesis, which mainly contains transcription factors, and we highlighted its role in retinal neuron differentiation.

Neural stem cells in the retina

Breakthrough studies have recently rejected the long-standing belief that neuronal tissue is incapable of regeneration. Recently indeed, adult neural stem cells have been isolated from the hippocampus and the subventricular zone of the adult mammalian brain. Stem cells are defined as cells having the ability to self-renew, and to differentiate into multiple phenotypic lineages. Comprehensive analysis of stem cells properties is of upmost importance to explore their therapeutic potential. Transplantation of neural stem cells may for instance regenerate damaged spinal cord or brain tissues. A molecular characterization of stem cells would also be valuable for cancer research due to their high similarities with some tumoral cells named “cancer stem cell”. The origin of these cells is not yet known, but they could derive from dysfunctional stem cells.
The amphibian and fish adult retinas continues to grow throughout the animal life. New retinal cells are continuously generated , through the activity of stem cells located in a region known as the ciliary marginal zone. Recently, it has been discovered that adult avian and mammalian retinas, including human ones, also contain neural stem cells, although quiescent in vivo. Retinal stem cell research is clearly of interest for clinicians, who are aiming to employ stem cells as a potential tool to treat retinal dystrophies, through their transplantation into damaged retina. The molecular characterization of retinal stem cell identity and properties remains however at a starting point. Studying the function of known signaling pathways in these cells and identifying specific novel markers of retinal stem cells is thus of first importance to understand the mechanisms underlying their self-renewal, multipotency and plasticity. This fundamental aspect of stem cell biology also constitutes an essential basic knowledge for therapeutic and cancer research. Our model is the Xenopus retina, which contains retinal stem cells in a well identified niche in the ciliary marginal zone. This particularity is obviously favourable to foresee in vivo experimental strategies. Our recent work on Hedgehog signalling demonstrated its role in the control of cell cycle kinetics of stem cells and progenitors of the retina. Along the same line, our objective is now to unravel mechanisms underlying the action of other signalling pathways and the interactions they establish to modulate retinal stem cell and precursor proliferation.

COLLABORATIONS

- William A. Harris, Cambridge University, UK

- Eric Bellefroid, Université de Bruxels, Belgium

- Kris Vleminckx, Ghent University, Belgium

-Tomas Pieler, Gottingen University, Germany

- Nicolas Pollet and Odile Bronchain, our department, University Paris XI, Orsay, France