PgmNr Z6108: Profiling the active genomic elements of progenitor cells in the zebrafish optic tectum and telencephalon.

Authors:
R. ESPOSITO 1,2 ; A. Heuzé 1 ; L. Bally-Cuif 2 ; JS. Joly 1


Institutes
1) CNRS Neuro-PSI, CASBAH group, Gif-sur-Yvette, FR; 2) CNRS Neuro-PSI, Zebrafish Neurogenetics group, Gif-sur-Yvette, FR.


Abstract:

Zebrafish, as other teleost fish, display a remarkable capacity to produce neurons throughout life. This process arises from neurogenic niches distributed along the rostro-caudal axis of the brain, responsible for both constitutive neurogenesis and neuronal repair after injuries. Different progenitor subtypes, some exhibiting Neural Stem Cells (NSC)-like features, have been distinguished in adult neurogenic zones: self-renewing radial glial cells (RG; i.e. in the dorsal telencephalon, hypothalamus) and neuroepithelial-like cells (i.e. lateral and ventral telencephalon, optic tectum, cerebellum), which can also contribute to the generation of RG pools. The main interest of our laboratories is to dissect the genetic and molecular mechanisms controlling adult neurogenesis in the zebrafish telencephalon and optic tectum. To this aim, one approach consists in investigating the epigenetic state characterizing cell proliferation, quiescence and differentiation within the aforementioned neurogenic niches. Indeed, epigenetic mechanisms changing chromatin compaction and its nucleoprotein structure are part of processes controlling cell state, as biologically active genomic elements (e.g. enhancers, promoters, etc) need to be accessible to the transcription machinery, whereas inactive regions are sequestered in the hierarchical chromatin packaging. Therefore, the analysis of chromatin accessibility can provide information on the state or the potential of a cell in a given context. We are profiling the active genomic elements involved in zebrafish neurogenesis using ATAC-seq, a relatively new chromatin accessibility assay, which can be applied also to a very limited amount of starting material (5K cells). In order to isolate by FACS the cells to analyse, we are using fish lines in which specific regulatory regions drive the expression of GFP and/or RFP in the appropriate cells: glial and neuroepithelial progenitors, proliferating cells and differentiated neurons, for epigenomic profiling in the optic tectum, and quiescent RG, activated RG and transient progenitors, for the telencephalon. Our work should allow identifying in vivo the regulatory logic that specifies the identity and/or the different cell states/types (from progenitors to neurons) operating in two important neurogenic zones in the zebrafish adult brain, and will also permit a comparison between these two territories.