Revealing the cellular and transcriptome dynamics underlying vertebrate neural development and regeneration.

• Applicants: Professor Dr. Michael Brand; Dr. Christian Lange
• Subject Area: Developmental Neurobiology ; Developmental Biology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433117914

• Final Report Year: 2025

Final Report Abstract

Unlike humans, zebrafish can regenerate brain lesions in adult stages by replacement of lost neurons through induced neurogenesis from glial precursors. However, on the molecular level it is still unclear i) how selective, regeneration-specific induction of neurogenesis is accomplished, ii) how neuronal cell type specification is regulated in regeneration, and iii) whether these mechanisms are conserved or differ between brain development and regeneration. We used single cell mRNA sequencing to define the heterogeneity and activation mechanisms of radial glia (in the forebrain) and the Mueller glia (in the retina) as neuronal precursors in development and regeneration. Further, we combined sequencing and lineage tracing technology to analyze cell fate potential and differentiation trajectories of precursor subpopulations to reveal their functional heterogeneity. Using these data, we investigated how the generation of diverse neuronal cell types is mirrored at the molecular level. Understanding these processes in the zebrafish, as a regeneration-competent vertebrate, potentially suggests therapeutic avenues for brain injury and neurodegeneration in patients.

Publications

• Reactive oligodendrocyte progenitor cells (re-)myelinate the regenerating zebrafish spinal cord. Development, 147(24).
  Tsata, Vasiliki; Kroehne, Volker; Wehner, Daniel; Rost, Fabian; Lange, Christian; Hoppe, Cornelia; Kurth, Thomas; Reinhardt, Susanne; Petzold, Andreas; Dahl, Andreas; Loeffler, Markus; Reimer, Michell M. & Brand, Michael
  
• Single cell sequencing of radial glia progeny reveals the diversity of newborn neurons in the adult zebrafish brain. Development, 147(1).
  Lange, Christian; Rost, Fabian; Machate, Anja; Reinhardt, Susanne; Lesche, Matthias; Weber, Anke; Kuscha, Veronika; Dahl, Andreas; Rulands, Steffen & Brand, Michael
  
• Single‐cell transcriptome analysis reveals thyrocyte diversity in the zebrafish thyroid gland. EMBO reports, 21(12).
  Gillotay, Pierre; Shankar, Meghna; Haerlingen, Benoit; Eski, Sema Elif; Pozo‐Morales, Macarena; Garteizgogeascoa, Inés; Reinhardt, Susanne; Kränkel, Annekathrin; Bläsche, Juliane; Petzold, Andreas; Ninov, Nikolay; Kesavan, Gokul; Lange, Christian; Brand, Michael; Lefort, Anne; Libert, Frédérick; Detours, Vincent; Costagliola, Sabine & Sumeet Pal, Singh
  
• Vertebrate brain regeneration – a community effort of fate-restricted precursor cell types. Current Opinion in Genetics & Development, 64, 101-108.
  Lange, Christian & Brand, Michael
  
• A switch in pdgfrb cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord. Developmental Cell, 56(4), 509-524.e9.
  Tsata, Vasiliki; Möllmert, Stephanie; Schweitzer, Christine; Kolb, Julia; Möckel, Conrad; Böhm, Benjamin; Rosso, Gonzalo; Lange, Christian; Lesche, Mathias; Hammer, Juliane; Kesavan, Gokul; Beis, Dimitris; Guck, Jochen; Brand, Michael & Wehner, Daniel
  
• Vision-related convergent gene losses reveal SERPINE3’s unknown role in the eye. eLife, 11.
  Indrischek, Henrike; Hammer, Juliane; Machate, Anja; Hecker, Nikolai; Kirilenko, Bogdan; Roscito, Juliana; Hans, Stefan; Norden, Caren; Brand, Michael & Hiller, Michael
  
• Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation. Development, 150(19).
  Harish, Rohit Krishnan; Gupta, Mansi; Zöller, Daniela; Hartmann, Hella; Gheisari, Ali; Machate, Anja; Hans, Stefan & Brand, Michael
  
• Single cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration. openRxiv.
  Celotto, Laura; Rost, Fabian; Machate, Anja; Bläsche, Juliane; Dahl, Andreas; Weber, Anke; Hans, Stefan & Brand, Michael
  
• Inflammation is a critical factor for successful regeneration of the adult zebrafish retina in response to diffuse light lesion. Frontiers in Cell and Developmental Biology, 12.
  Bludau, Oliver; Weber, Anke; Bosak, Viktoria; Kuscha, Veronika; Dietrich, Kristin; Hans, Stefan & Brand, Michael
  
• Restoration of cone-circuit functionality in the regenerating adult zebrafish retina. Developmental Cell, 59(16), 2158-2170.e6.
  Abraham, Evelyn; Hartmann, Hella; Yoshimatsu, Takeshi; Baden, Tom & Brand, Michael