Molecular mechanisms of nervous system development and maintenance in zebrafish

 

     Principal Investigator (PI): Sepand Rastegar

     tel.: +49 721 608 22507
     fax: +49 721 608 23354
     email: sepand.rastegar∂kit.edu



 

 

 

Neurons are the building blocks of our nervous system. They receive, process, and transfer information, allowing us to make important decisions and carry out everyday tasks. In the adult mammalian brain, neurons are formed from neuronal stem cells (NSCs) which are found in only two or three restricted neurogenic niches located in the forebrain. These neurons reproduce rarely and therefore the mammalian brain has a limited capacity to replace neurons, e.g. after an injury. Consequently, in humans, neurodegenerative diseases are incurable and result in progressive degeneration and death of nerve cells, leading to severe conditions such as dementia and ataxia.

Our aim is to use the zebrafish as a model to understand how adult neurogenesis and regeneration works in vertebrates. In contrast to mammals, the zebrafish has an extensive ability to develop new neurons in all regions of the brain and can efficiently repair its nervous system after injury. As a long-term goal, our research could explain how to reactivate these mechanisms and re-instruct neurogenesis from NSCs after brain injury.

Our approach is to assess the regulatory networks involved in neural stem cell quiescence and activation, under both normal physiological conditions as well as upon brain injury. We employ genome-wide techniques such as RNA-, CAGE- and single cell sequencing, candidate gene approaches, as well as molecular and cellular biology and microscopy techniques.
In order to have a more comprehensive view of neural development as a whole, we also investigate the early development of neurons in the spinal cord of zebrafish embryos at different stages.

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.

 

Recent publications

Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish. Baranasic, Hörtenhuber, Balwierz, Zehnder, Mukarram, Nepal, Várnai, Hadzhiev, Jimenez-Gonzalez, Li, Wragg, D’Orazio, Relic, Pachkov, Díaz, Hernández-Rodríguez, Chen1, Stoiber, Dong, Stevens, Ross, Eagle, Martin, Obasaju, Rastegar, S. et al., 2022. Nature Genetics (in Press).

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

Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon. Zhang, G.; Lübke, L.; Chen, F.; Beil, T.; Takamiya, M.; Diotel, N.; Strähle, U.; Rastegar, S. 2021. Cells, 10 (10), Art.-Nr.: 2794. doi:10.3390/cells10102794.

Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury. Gourain, V.; Armant, O.; Lübke, L.; Diotel, N.; Rastegar, S.; Strähle, U. 2021. Frontiers in neuroscience, 15, Article no: 671249. doi:10.3389/fnins.2021.671249.

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

Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals. Diotel, N.; Lübke, L.; Strähle, U.; Rastegar, S. 2020. Frontiers in neuroscience, 14, Art.-Nr.: 568930. doi:10.3389/fnins.2020.568930.

Bone morphogenetic protein signaling regulates Id1-mediated neural stem cell quiescence in the adult zebrafish brain via a phylogenetically conserved enhancer module. Zhang, G.; Ferg, M.; Lübke, L.; Takamiya, M.; Beil, T.; Gourain, V.; Diotel, N.; Strähle, U.; Rastegar, S. 2020. Stem cells, 38, 875–889. doi:10.1002/stem.3182.

Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair. Rastegar, S.; Parimisetty, A.; Cassam Sulliman, N.; Narra, S. S.; Weber, S.; Rastegar, M.; Viranaicken, W.; Couret, D.; Planesse, C.; Strähle, U.; Meilhac, O.; Lefebvre d’Hellencourt, C.; Diotel, N. 2019. The journal of comparative neurology, 527 (14), 2317–2333. doi:10.1002/cne.24669.

The HMG box transcription factors Sox1a and Sox1b specify a new class of glycinergic interneuron in the spinal cord of zebrafish embryos. Gerber, V.; Yang, L.; Takamiya, M.; Ribes, V.; Gourain, V.; Peravali, R.; Stegmaier, J.; Mikut, R.; Reischl, M.; Ferg, M.; Rastegar, S.; Strähle, U. 2019. Development, 146 (4), dev172510. doi:10.1242/dev.172510.