Neurons are the building blocks of our nervous system. They receive and integrate the sensory information that controls our daily behaviour. The main objective of our team is to elucidate the molecular mechanisms involved in generation, differentiation, specification, and regeneration of neurons. We are particularly interested in deciphering the signals and gene regulatory networks that orchestrate these processes of neurogenesis. We believe that this knowledge will help guide the formation of engineered neuronal tissues in vitro and have implications for the development of regenerative therapies.

To study how neuronal diversity is generated in the vertebrate central nervous system, we are using the embryonic zebrafish spinal cord as a model, due to its relatively simple neural network and evolutionarily conserved cell population.

To understand how neurogenesis and regeneration work in vertebrates, we use the zebrafish brain as a model. Unlike mammals, adult zebrafish have a great capacity to develop new neurons in all regions of the brain and can efficiently repair their nervous system after injury. As a long-term goal, our research might explain how to reactivate regenerative mechanisms and re-instruct neurogenesis from neural stem cells after brain injury.

We are using genomic techniques such as RNA-seq, CAGE-seq and single cell sequencing, as well as loss/gain of function approaches to identify and characterise candidate genes involved in neurogenesis and regeneration. As DNA regulatory elements are important sites of signal integration, we use a combined strategy merging data from ATAC-seq, ChIP-seq, cross-species sequence conservation, transgenesis and mutational approaches to identify relevant regulatory elements of key genes for neuronal development and maintenance. 

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).

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.

Zebrafish Adult Telencephalon Stab Wound Injury 

https://www.jove.com/de/v/51753/stab-wound-injury-zebrafish-adult-telencephalon-method-to-investigate
 

Baranasic D, et al., 2022. Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nature Genetics. 2022 July (/doi.org/10.1038/s41588-022-01089-w).

Lübke L, Zhang G, Strähle U, Rastegar S. mdka Expression Is Associated with Quiescent Neural Stem Cells during Constitutive and Reactive Neurogenesis
in the Adult Zebrafish Telencephalon. Brain Sci. 2022 Feb 18;12(2):284. doi: 10.3390/brainsci12020284.

Zhang G, Lübke L, Chen F, Beil T, Takamiya M, Diotel N, Strähle U, Rastegar S. Neuron-radial glial cell communication via BMP/Id1 signaling maintains the regenerative capacity of the adult zebrafish telencephalon. Cells. 2021 Oct 19;10(10):2794. doi: 10.3390/cells10102794.

Gourain V, Armant O, Lübke L, Diotel N, Rastegar S, Strähle U. Multi-dimensional transcriptome analysis reveals modulation of cholesterol metabolism as highly integrated response to brain injury.  Front Neurosci. 2021 May 14;15:671249. doi: 10.3389/fnins.2021.671249. eCollection 2021.

Ghaddar, B., Lübke, L., Couret, D., Rastegar S#., Diotel, N. (2021) Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals after Injury. Cells. 2021 Feb 14;10(2):391. doi: 10.3390/cells10020391.

Diotel, N., Lübke, L., Strähle, U., Rastegar, S. (2020) Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals. 
Frontiers in neuroscience. Front Neurosci. 2020 Sep 23;14:568930. doi: 10.3389/fnins.2020.568930. eCollection 2020.

Zhang G, Ferg M, Lübke L, Takamiya M, Beil T, Gourain V, Diotel N, Strähle U, Rastegar S. Bone morphogenetic protein signaling regulates Id1-mediated neural stem cell quiescence in the adult zebrafish brain via a phylogenetically conserved enhancer module. Stem Cells. (2020) Apr 3. doi: 10.1002/stem.3182.

Rastegar, S., Parimisetty, A., Cassam-Sulliman, N., Narra Sai, S., Weber, S., Rastegar, M., Viranaicken, W., Couret, D., Planesse, C., Strähle, U., Meilhac, O., Lefebvre d'Hellencourt, C., Diotel, N. (2019) Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair. The Journal of comparative neurology. 527(14):2317-2333.

Gerber V, Yang L, Takamiya M, Ribes V, Gourain V, Peravali R, Stegmaier J, Mikut R, Reischl M, Ferg M, Rastegar S#, Strähle U. The HMG box transcription factors Sox1a and b specify a new class of glycinergic interneurons in the spinal cord of zebrafish embryos. Development. 2019 Feb 20;146(4). pii: dev172510. doi: 10.1242/dev.172510.

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