Michael Brand - Patterning and Regeneration of the Vertebrate Brain

Previous and current research

A fundamental problem in neurobiology is how the multitude of different cells and their connections are generated from their precursors, or stem cells. We have studied extensively how embryonic neural precursor cells at the border between midbrain and hindbrain (MHB) act as organizers of cell fate onto the surrounding cells, which eventually form the midbrain and cerebellum. We also study which signals determine where the MHB organizer forms initially. Fgf8 is absolutely required for MHB organizing activity. For instance, zebrafish acerebellar mutants have no functional Fgf8, and hence lack a cerebellum and proper polarity in the midbrain. In genetic, cell biological and biophysical studies, we are unraveling how secreted Fgf signals exert their function at the MHB and in other embryonic organizer cell populations.

More recently we have probed for a possible role of organizer-associated signaling molecules also in the adult brain. We find that in contrast to mammals, adult zebrafish brains retain an amazing number of active neural stem cells at all times, and in very discreet spatial domains. Given the well known ability of teleost brains to repair damage, and the lack thereof in mammalian brains, stem cell based regeneration studies in fish may provide clues which mechanisms need to be activated to stimulate CNS regeneration also in mammalian brains. Indeed numerous new neurons of different subtypes are produced in the adult zebrafish brain, providing an ideal genetically and experimentally tracktable system for understanding brain repair processes.

Future prospects and goals

organizer-dependent patterning and differention processes in the embryonic and adult vertebrate brain
understanding stem cell activity and control in the adult CNS of a regenerating vertebrate

Selected publications

Yu, S.R., Burkhardt, M., Nowak, M., Ries, J., Petrášek, Z., Scholpp, S., Schwille, P. and Brand, M. (2009): FGF8 morphogen gradient is formed by a source-sink mechanism with freely-diffusing molecules. Nature, in press.

Picker, A., Cavodeassi, F., Machate, A., Abe, G., Kawakami, K., Wilson, S. and Brand, M. (2009): Three Fgf Signals Coordinate Pattern Formation and Epithelial Morphogenesis in the Neural Retina. PLOS Biology, in press.

Ries, J., Yu, S. R., Burkhardt, M., Brand,M. and Schwille, P.(2009): Modular scanning FCS quantifies ligand-receptor interactions in live multicellular organisms. Nature Methods, Aug. 2 PMID: 19648917.

Hans, S., Kaslin, J., Freudenreich, D. and Brand, M. (2009): Temporally-controlled Site-specific Recombination in Zebrafish. PLoS One, 4(2):e4640.

Kaslin, J., Ganz, J., Geffarth, M., Grandel, H., Hans, S. and Brand M. (2009): Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche. J Neuroscience, 29(19):6142-6153

Rhinn, M., Lun, K., Arendt, R., Werner,M. and *_Brand, M._* (2009): Zebrafish /gbx1/ refines the Midbrain-Hindbrain Boundary border and mediates the Wnt8 posteriorization signal. Neural Development, 2;4:12.

Schenck, A., Goto-Silva, L., Collinet, C., Rhinn, M., Giner, A., Habermann, B., Brand, M. and Zerial, M. (2008): The endosomal protein APPL1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell 133, 486-497.

Kaslin, J., Ganz, J., and Brand, M. (2008): Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain. Philos Trans R Soc Lond B Biol Sci, Stem Cell Issue, Feb., 1-23

Picker, A., Roellig, D., Oates, A. and *_Brand, M._* (2008): Tissue micromanipulation in the zebrafish embryo. Methods Mol. Biol., 2009;546:153-172

Grandel, H., Kaslin, J., Ganz, J., Wenzel, I., and Brand, M. (2006): Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate. Developmental Biology, 295(1):263-277.

Rhinn, M., Lun, K., Luz, M., Werner, M., Brand, M. (2005): Positioning of the midbrain-hindbrain boundary organizer through global posteriorisation of the neuroectoderm mediated by Wnt8 signaling. Development 132, 1261-1272.

Reim, G., Mizoguchi, T., Stainier, D.Y., Kikuchi, Y. and Brand, M (2004): The POU domain protein Spg (Pou2/Oct4) is essential for endoderm formation in cooperation with the HMG domain protein Casanova.
Developmental Cell 6, 91-101.

Scholpp, S. and Brand, M. (2004): Endocytosis controls spreading and effective signaling range of Fgf8. Current Biology 14 (20): 1834-1841.

Michael Brand

1989: PhD, University of Cologne

Postdoctoral work at University of California San Francisco and the MPI for Developmental Biology, Tübingen

1995-1999: Group Leader at the University of Heidelberg

since 2000: Group Leader at MPI-CBG

since 2003: Professor of Developmental Genetics, TU Dresden

since 2005: Director, Biotechnological Center, TU Dresden

since 2005: Speaker, DFG Research Center / Cluster of Excellence for Regenerative Therapies, CRTD