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

Group Members

List of group members

Recent Publications

2009

Picker A, Cavodeassi F, Machate A, Bernauer S, Hans S, Abe G, Kawakami K, Wilson SW, Brand M. (2009) Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina. PLoS Biol. Epub 2009 Oct 13.

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, Sep 24;461(7263):533-6

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.

Rhinn M, Lun K, Ahrendt R, Geffarth M, Brand M. (2009) Zebrafish gbx1 refines the midbrain-hindbrain boundary border and mediates the Wnt8 posteriorization signal. Neural Dev. 2009 Apr 2;4:12.

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, May 13;29(19):6142-53. PMID: 19439592 [PubMed - in process]

Picker A, Roellig D, Pourquié O, Oates AC, Brand M. (2009) Tissue micromanipulation in zebrafish embryos. Methods Mol Biol. 546:153-72.

Hans, S., Kaslin, J., Freudenreich, D., and Brand, M. (2009). Temporally-controlled Site-specific Recombination in Zebrafish. PLoS ONE. 2009;4(2):e4640. Epub 2009 Feb 27.

2008

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. 2008 May 2;133(3):399-400.

Kaslin J, Ganz J, Brand M. (2008). Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain. Philos Trans R Soc Lond B Biol Sci. 29;363 (1489):101-122.

2007

Scholpp, S. and Brand, M. (2007) Regionalisation of the neural tube: a balance between organizers and competence fields. New Encyclopedia for Neuroscience 2007, Ed. Larry Squire, UCSD School of Medicine, USA.

Wendl T, Adzic D, Schoenebeck JJ, Scholpp S, Brand M, Yelon D, Rohr KB. (2007). Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals. Development 134(15):2871-2879.

Erickson, T., Scholpp, S., Brand, M., Moens, C. B., and Waskiewicz, A. J. (2007). Pbx proteins cooperate with Engrailed to pattern the diencephalon-midbrain boundary. Developmental Biology 301, 504-517.

Funfak, A. Brösing, A., Brand, M. and Köhler, J.M. (2007). Micro-fluid segment technique for screening and development studies on Danio rerio embryos. Royal Soc Chemistry LOC, 7(9):1132-1138.

Erickson, T., Scholpp, S., Brand, M., Moens, C. B., and Waskiewicz, A. J. (2007). Pbx proteins cooperate with Engrailed to pattern the diencephalon-midbrain boundary. Developmental Biology, Jan 15;301(2):504-17. doi: 10.1016/j.ydbio.2006.08.022

2006

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.

Reim, G., and Brand, M. (2006). Maternal control of vertebrate dorso-ventral axis formation and epiboly by the POU domain protein Spg/Pou2/Oct4. Development, 133(14):2757-2770.

Scholpp, S., Wolff, O. , Brand, M. and Lumsden, A. (2006). Hedgehog signalling from the Zona Limitans Intrathalamica orchestrates differentiation of the zebrafish diencephalon. Development 133, 855-864.

Rhinn, M., Picker, A., and Brand, M. (2006). Global and local mechanisms of forebrain and midbrain patterning. Curr Opin Neurobiology 16, 1-8.

Langenberg, T., Dracz, T., Oates, A.C., Heisenberg, C.P. and Brand, M. (2006): Analysis and visualization of cell movement in the developing zebrafish brain. Developmental Dynamics, 235(4); 928-933.

Scholpp, S. and Brand, M. (2006) Regionalisation of the neural tube: a balance between organizers and competence fields. New Encyclopedia for Neuroscience 2007, Ed. Larry Squire, UCSD School of Medicine, USA. Submitted.

2005

Picker, A. and Brand, M. (2005): Fgf-signals from a novel signaling center determine axial patterning of the prospective neural retina. Development 132 (22):4951-4962

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.

Winkler, S., Schwabedissen, A., Backasch, D., Bökel, C., Seidel, C., Bönisch, S., Fürthauer, M., Kuhrs, A., Cobreros, L, Brand, M. and González-Gaitán, M. (2005). Target-selected mutant screen by TILLING in Drosophila. Genome Research, 15(5):718-723.

Langenberg, T.L. and Brand, M. (2005). Lineage restriction maintains a stable organizer cell population at the zebrafish midbrain-hindbrain boundary. Development, 132(14):3209-3216.

Research Support