Previous and current research

A fundamental problem in neurobiology is how the multitude of different cells of the brain are generated from their precursors, or stem cells. We study the underlying mechanisms during vertebrate brain development and regeneration. We ask, for instance, how neural stem cells give rise to and maintain the adult brain, during normal homeostasis and during regeneration of the brain. Because zebrafish have a spectacular ability to regenerate and well developed genetics and molecular biology tools, they are particularly well-suited for these studies.

We studied 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, and which signals determine where the MHB organizer forms initially. The signaling molecule 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 study how secreted Fgf signals exert their function at the MHB and in other embryonic organizer cell populations, and how Fgf gradients form in the embryonic neural primordium (left panel). 

We also study organizer-associated signaling molecules in the adult brain. In contrast to mammals, adult zebrafish brains retain an amazing number of active neural stem cells throughout, in very discrete spatial domains (right panel). Numerous new neurons of different subtypes are produced in the adult zebrafish brain, providing an ideal genetically and experimentally tractable system for understanding brain repair processes. Using CNS lesion paradigms, transgenics and Cre-loxP technology, we ask by genome-wide methods what controls the ability of adult neural stem cells to repair damage. Stem cell based regeneration studies in fish may thus provide clues how CNS regeneration can be stimulated also in mammalian brains.

Recently we established a new open access database, the zebrafish CreZoo (http://crezoo.crt-dresden.de), which contains novel CreER^T2-driver lines that express CreER^T2 in several tissues.

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

2012

Kizil, C., Dudczig, S., Kyritsis, N., Machate, A., Blaesche, J., Kroehne, V., Brand, M. (2012). The chemokine receptor cxcr5 regulates the regenerative neurogenesis
response in theadult zebrafish brain. Neural Dev. 2012 Jul 23;7:27. doi: 10.1186/1749-8104-7-27

Kyritsis, N., Kizil, C., Zocher, S. Kroehne, V., Kaslin, J., Freudenreich, D., Iltzsche, A., Brand, M. (2012). Acute inflammation initiates the regenerative response in the adult zebrafish brain. Science, DOI 10.1126.science.1228773.
Abstract: http://www.sciencemag.org/cgi/content/abstract/science.1228773?ijkey=87dq1v5XQHZAM&keytype=ref&siteid=sci
Reprint: http://www.sciencemag.org/cgi/rapidpdf/338/6112/1353?ijkey=87dq1v5XQHZAM&keytype=ref&siteid=sci
Full text: http://www.sciencemag.org/cgi/content/full/science.1228773?ijkey=87dq1v5XQHZAM&keytype=ref&siteid=sci

Kizil, C. N Kyritsis, S Dudczig, V Kroehne, D Freudenreich, Kaslin, J and  M Brand (2012). Regenerative neurogenesis from neural progenitor cells requires injury-induced expression of Gata3. Developmental Cell, in press, DOI 10.1016/j.devcel.2012.10.014.

Grandel, H. and Brand, M. (2012). Comparative aspects of adult neural stem cell activity in vertebrates. Development, Genes and Evolution, in press.

Kroehne, V. and Brand, M. (2012). The cellular basis of constitutive and regenerative neurogenesis in the adult zebrafish brain. Cell News Vol. 38, 1/2012, 12-16.

Hochmann, S., Kaslin, J., Hans, S., Weber, A., Machate, A., Geffarth, M., Funk, R. and Brand, M. (2012). Fgf signaling is required for photoreceptor maintenance in the adult zebrafish retina. PLoS One 7(1): e30365. doi:10.1371/journal.pone.0030365.

Kaslin J, and Brand M (2012) Cerebellar development and neurogenesis in zebrafish. In: Manto M, Gruol D, Schmahmann J, Koibuchi N, Rossi F, editors. Handbook of the Cerebellum and Cerebellar Disorders. New York, Berlin, Heidelberg: Springer.

Kizil C, Kaslin J, Kroehne V, Brand M (2012). Adult neurogenesis and brain regeneration in zebrafish. <http://www.ncbi.nlm.nih.gov/pubmed/21595047> Dev Neurobiol. 72(3): 429-461.

Ganz, J., Kaslin, J. and Brand, M. (2012). Subdivisions of the adult zebrafish telencephalon based on molecular marker analysis. J. Comp. Neurol., 520(3):633-655.

Mahabaleshwar, H., Tarbashevich, K., Nowak, M. Brand, M. and Raz, E. (2012). β-arrestin control of late endosomal sorting facilitates decoy receptor function and chemokine gradient formation. Development 139 (16):2897-2902.

2011

Kizil C, Brand M (2011) Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells. PLoS ONE 6(11): e27395. doi:10.1371/journal.pone.0027395

Volker Kroehne, Dorian Freudenreich, Stefan Hans, Jan Kaslin and Michael Brand (2011). Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development 138, in press.

Nowak, M., Yu, Shuizi Rachel, Gupta, Mansi, Machate, Anja and Brand, Michael (2011): Interpretation of the Fgf8 morphogen gradient is regulated by endocytic trafficking. Nature Cell Biology 13(2):153-158.

Knopf, Franziska, Christina Hammond, Avinash Chekuru, Thomas Kurth, Stefan Hans, Christopher W. Weber, Gina Mahatma, Shannon Fisher, Michael Brand, Stefan Schulte-Merker and Gilbert Weidinger (2011). Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Dev. Cell, 17;20(5):713-724.

Boldajipour, Bijan, Katsiaryna Tarbaschevicha, Maria Doitsidou, Cedric Laguric, Rachel Shuizu Yu, Jonas Riese, Karin Dumstreib, Julia Dörriesb, Esther-Maria Messerschmidta, Petra Schwille, Michael Brand, Hugues Lortat-Jacobc, Erez Raz (2011). A role for biased receptor recognition in chemokine subfunctionalization and evolution. Development 138, in press.

Jászai, József,  Christine A. Fargeas, Sylvi Graupner, Elly M. Tanaka, Michael Brand, Wieland B. Huttner and Denis Corbeil (2011). Distinct and conserved prominin-1/CD133–positive retinal cell populations identified across species. PLoS One, 6(3):e17590.

Dahmann, C, Oates, AC, Brand, M (2011) Boundary formation and maintenance in tissue development. Nature Review Genetics, 12(1):43-55.

Grandel, H. and Brand, M. (2011). Zebrafish limb development is triggered by a retinoic acid signal during gastrulation. Developmental Dynamics. 240(5):1116-1126.

Hans, S., Freudenreich, D., Geffarth, M., Kaslin, J., Machate, A. and  Michael Brand (2011). Generation of a non-leaky heat shock-inducible Cre line for conditional Cre/lox strategies in zebrafish. Developmental Dynamics 240(1):108-115.

Winkler, S., Gscheidel, N., Brand, M. (2011). Mutant generation in vertebrate model organisms by TILLING. In: Vertebrate Embryogenesis: Methods and Protocols, Methods in Molecular Biology Series. .

2010

Ganz J., Kaslin J., Hochmann S., Freudenreich D., Brand M. (2010) Heterogeneity and Fgf dependence of adult neural progenitors in the zebrafish telencephalon. GLIA, 58(11):1345-1363

Antos, Christopher L; and Brand, Michael (2010) Regeneration of Organs and Appendages in Zebrafish: A Window into Underlying Control Mechanisms. In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester http://www.els.net/ [DOI: 10.1002/9780470015902.a0022101]

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