Molecular mechanisms of nervous system development and maintenance in zebrafish

Neurons on zebrafish
Transverse sections (B) across zebrafish adult brain (A). C, D, E, F expression of sox1a (red) in telencephalon (C, D), optic tectum (E), optic tectum/cerebellum (F). Neurons (G) and radial glial cells (H) in the zebrafish telencephalon. Neurons in zebrafish parenchyma (G) and radial glial cells (blue/green) at the ventricular zone (H). Olfactory bulb (ob), telencephalon (tel), optic tectum (ot).

Neurons serve as the fundamental building blocks of our nervous system, playing a crucial role in receiving and integrating sensory information that influences our daily behaviour. Our team's primary objective is to uncover the molecular mechanisms underlying the generation, differentiation, specification, and regeneration of neurons. We have a particular interest in unravelling the intricate signals and gene regulatory networks that orchestrate the processes of neurogenesis. We firmly believe that this knowledge will provide valuable insights for the development of engineered neuronal tissues in vitro and contribute to advancements in regenerative therapies.

To investigate the generation of neuronal diversity within the vertebrate central nervous system, we employ the embryonic zebrafish spinal cord as a model system. This choice is driven by its relatively simple neural network and the evolutionarily conserved cell population it offers.

Furthermore, to gain a comprehensive understanding of neurogenesis and regeneration in vertebrates, we utilize the zebrafish brain as a model organism. Unlike mammals, adult zebrafish possess a remarkable capacity to generate new neurons throughout all regions of the brain and exhibit efficient nervous system repair mechanisms following injury. Our long-term research goals aim to elucidate the reactivation of regenerative mechanisms and the reprogramming of neurogenesis from neural stem cells after brain injury.

Our investigations rely on genomic techniques such as RNA-seq, CAGE-seq, and single-cell sequencing. Additionally, we employ loss/gain of function approaches to identify and characterize candidate genes involved in neurogenesis and regeneration. Recognizing the significance of DNA regulatory elements as pivotal sites of signal integration, we adopt a combined strategy that integrates data from ATAC-seq, ChIP-seq, cross-species sequence conservation, transgenesis, and mutational approaches. This comprehensive approach allows us to identify relevant regulatory elements associated with key genes responsible for neuronal development and maintenance. 

Expression of gata2a (red) and sox1a (green)
Expression of gata2a (red) and sox1a (green) in a zebrafish double transgenic line. The magnified region shows the expression of gata2a and sox1a in the interneurons of the zebrafish embryo spinal cord.

 

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