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. 

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
 

1: Chen F, Köhler M, Cucun G, Takamiya M, Kizil C, Cosacak MI, Rastegar S.
sox1a:eGFP transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons. iScience. 2023 Jul 11;26(8):107342. doi: 10.1016/j.isci.2023.107342. PMID: 37529101; PMCID: PMC10387610.

2: Cucun G, Köhler M, Pfitsch S, Rastegar S.
Insights into the mechanisms of neuron generation and specification in the zebrafish ventral spinal cord. FEBS J. 2023 Jul 27. doi: 10.1111/febs.16913. Epub ahead of print. PMID: 37498183. 

3: Baranasic D, Hörtenhuber M, Balwierz PJ, Zehnder T, Mukarram AK, Nepal C, Várnai C, Hadzhiev Y, Jimenez-Gonzalez A, Li N, Wragg J, D'Orazio FM, Relic D, Pachkov M, Díaz N, Hernández-Rodríguez B, Chen Z, Stoiber M, Dong M, Stevens I, Ross SE, Eagle A, Martin R, Obasaju O, Rastegar S, McGarvey AC, Kopp W, Chambers E, Wang D, Kim HR, Acemel RD, Naranjo S, Łapiński M, Chong V, Mathavan S, Peers B, Sauka-Spengler T, Vingron M, Carninci P, Ohler U, Lacadie SA, Burgess SM, Winata C, van Eeden F, Vaquerizas JM, Gómez-Skarmeta JL, Onichtchouk D, Brown BJ, Bogdanovic O, van Nimwegen E, Westerfield M, Wardle FC, Daub CO, Lenhard B, Müller F.
Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nat Genet. 2022 Jul;54(7):1037-1050. doi: 10.1038/s41588-022-01089-w. Epub 2022 Jul 4. PMID: 35789323; PMCID: PMC9279159.

4: Lübke L, Zhang G, Strähle U, Rastegar S.
mdkaExpression 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. PMID: 35204047; PMCID: PMC8870249.

5: 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 Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon. Cells. 2021 Oct 19;10(10):2794. doi: 10.3390/cells10102794. PMID: 34685774; PMCID:  PMC8534405.

6: Diotel N, Lübke L, Strähle U, Rastegar S.
Common and Distinct Features of Adult Neurogenesis and Regeneration in the Telencephalon of Zebrafish and Mammals. Front Neurosci. 2020 Sep 23;14:568930. doi: 10.3389/fnins.2020.568930. PMID: 33071740; PMCID: PMC7538694.

7: 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 Jul;38(7):875-889. doi: 10.1002/stem.3182. Epub 2020 Apr 11. PMID: 32246536.

8: Rastegar S, Parimisetty A, Cassam Sulliman N, Narra SS, Weber S, Rastegar M, Viranaicken W, Couret D, Planesse C, Strähle U, Meilhac O, Lefebvre d'Hellencourt C, Diotel N.
Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair. J Comp Neurol. 2019 Oct 1;527(14):2317-2333. doi: 10.1002/cne.24669. Epub 2019 Mar 29. PMID: 30843204.

9: 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 Sox1b specify a new class of glycinergic interneuron in the spinal cord of zebrafish embryos. Development. 2019 Feb 20;146(4):dev172510. doi: 10.1242/dev.172510. PMID: 30760481.

10: Rodriguez Viales R, Diotel N, Ferg M, Armant O, Eich J, Alunni A, März M, Bally-Cuif L, Rastegar S#, Strähle U.
The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon. Stem Cells.  015 Mar;33(3):892-903. doi: 10.1002/stem.1883. PMID: 25376791.

# Corresponding author