Michael Brand - Development and Regeneration of the Vertebrate Brain


1986: M.A., Harvard University, Diploma, University of Cologne

1989: PhD, University of Cologne

1990: Postdoctoral work at University of California San Francisco

1992: Helmholtz Fellow, MPI for Developmental Biology, Tübingen

1995-1999: Group Leader at the University of Heidelberg

2000-2006: Group Leader at MPI-CBG

since 2003:Professor of Developmental Genetics, TU Dresden

2005-2012: Director, Biotechnology Center, TU Dresden

2005 - 2014: Director, DFG Research Center / Cluster of Execellence 'Regenerative Therapies'
Vice-Speaker, SFB 655 - Cells into Tissues

A fundamental problem in neurobiology is how the multitude of different cells of the brain is generated from their precursors, or stem cells. We study the underlying mechanisms during vertebrate brain development and regeneration.   

In contrast to mammals, the central nervous system (CNS) of adult zebrafish retains a large number of active neural stem/progenitor cells producing numerous new neurons of different subtypes in discrete spatial domains. Moreover, the adult zebrafish CNS has a spectacular ability to regenerate after severe lesions. Combined with well-developed genetic and molecular biology tools, it therefore provides an ideally tractable system for understanding recruitment of stem cells during normal homeostasis and in the context of regeneration.

Using various CNS lesion paradigms, transgenesis, Cre/loxP technology and next generation sequencing we investigate which genes and pathways regulate adult neural stem cell activity and their ability to repair damage. We also address how the distribution of organizer-associated signalling molecules is propagated in the embryonic and adult CNS controlling the formation and maintenance of compartment boundaries.

Our studies will provide clues on how CNS regeneration can be stimulated also in mammalian brains and pave the way for stem cell based regenerative therapies against acute as well as chronic brain injury. 

Recently we established a new open access database, the zebrafish CreZoo (http://crezoo.crt-dresden.de), which contains novel CreERT2-driver lines that express CreERT2 in several tissues.

 

Ongoing Projects

Click here for more information about ongoing projects

 

Future prospects and goals

  • Identification of the molecular mechanisms that allow adult CNS regeneration in a regeneration-competent organism to rekindle regeneration in degenerative brain diseases and also in the mammalian CNS
  • organizer-dependent patterning and differentiation processes in the embryonic and adult vertebrate brain

 

Group Members

List of group members

List of alumni

 

Recent Publications

For a full list of publications and citation information, please see
www.researcherid.com/rid/A-5509-2010

 

Publications 2016/2015

Ganz, J. and Brand, M. (2016). Adult Neurogenesis in Fish. Cold Spring Harb Perspect Biol. Eds. Gage, Kempermann, Song. Cold Spring Harbor Laboratory Press. doi: 10.1101/cshperspect.a019018. PMID: 26747664.

Kaslin, J. and Brand, M. (2016). The Zebrafish Cerebellum. In: Essentials of Cerebellum and Cerebellar Disorders. A Primer For Graduate Students. In: D.L. Gruol et al. (eds.), Springer. DOI 10.1007/978-3-319-24551-5_56A

Jungke P, Hans S, Gupta M, Machate A, Zöller D, M. Brand (2016). Generation of a conditional lima1a allele in zebrafish using the FLEx switch technology. Genesis 54(1):19-28. doi: 10.1002/dvg.22909.

Arulmozhivarman, G., Stöter, M., Bickle, M., Kräter, M., Wobus, M., Ehninger, G., Stölzel, F., Brand, M., Bornhäuser, M., and Shayegi, N. (2016). In Vivo Chemical Screen in Zebrafish Embryos Identifies Regulators of Hematopoiesis Using a Semiautomated Imaging Assay. Journal of Biomolecular Screening, in press.

Paolini, A.; AL Duchemin, S Albadri, E Patzel, D Bornhorst, P Gonzalez Avalos, S Lemke, A Machate, M Brand, S Sel, V Di Donato, F Del Bene, Flavio R Zolessi, M Ramialison, and L Poggi (2015). Asymmetric inheritance of the apical domain and self-renewal of retinal ganglion cell progenitors depend on Anillin function. Development 142, 1-8. doi:10.1242/dev.118612

C. Antos, F. Knopf and M. Brand (2015). 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/A26051.

Hernandez-Bejarano, Maria; Gaia Gestri, Lana Spawls, Francisco Nieto-Lopez, Alexander Picker, Masazumi Tada, Michael Brand, Paola Bovolenta, Stephen W Wilson, and Florencia Cavodeassi (2015). Opposing Shh and Fgf signals initiate nasotemporal patterning of the retina. Development, 142(22):3933-3942.

Kizil, C.; Iltzsche, A.; Thomas, A.K.; Bhattarai, P.; Zhang, Y.; Brand, M. (2015). Efficient cargo delivery into adult brain tissue using short cell-penetrating peptides. PloS One, Apr 20;10(4):e0124073. doi: 10.1371/journal.pone.0124073.

Jungke, P., Hammer, J., Hans, S. and Brand, M. (2015). Isolation of novel CreERT2-driver lines in zebrafish using an unbiased gene trap approach. PLoS One 10(6): e0129072. doi:10.1371/journal.pone.0129072.


2014

Gaertner, Maria; Anke Weber, Peter Cimalla, Felix Köttig, Brand, M., Edmund Koch (2014). Towards a comprehensive eye model for zebrafish retinal imaging using full range spectral domain optical coherence tomography. Proc. SPIE 8934, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XVIII, 89342H; doi:10.1117/ 12.2037588

Kyritsis, N., Kizil, C. and Brand, M. (2014). Neuroinflammation and central nervous system regeneration in vertebrates. Trends in Cell Biology, doi:pii: S0962-8924(13)00137-2. 10.1016/j.tcb.2013.08.004

Ganz, Julia, Volker Kroehne, Dorian Freudenreich, Anja Machate, Michaela Geffarth, Ingo Braasch, Jan Kaslin, and M. Brand (2014). Subdivisions of the adult zebrafish pallium based on molecular marker analysis. F1000Research 2014, 3:308 (doi: 10.12688/f1000research.5595.1).

Kizil, C., Kuchler, B., Yan, J.J., Ozhan, G., Moro, E., Argenton, F., Brand, M., Weidinger, G., and Antos, C.L. (2014). Simplet/Fam53b is required for Wnt signal transduction by regulating beta-catenin nuclear localization. Development 141, 3529-3539.

 

2013

Weber A, Hochmann S, Cimalla P, Gärtner M, Kuscha V, Hans S, Geffarth M, Kaslin J, Koch E, Brand M. (2013). Characterization of light lesion paradigms and optical coherence tomography as tools to study adult retina regeneration in zebrafish. PLoS One. 8(11):e80483.

Gupta M, Brand M. (2013).  Identification and Expression Analysis of Zebrafish Glypicans during Embryonic Development. PLoS One. 8(11):e80824.

Shayegi N, Meyer C, Lambert K, Ehninger G, Brand M, Bornhäuser M. (2013).  CXCR4 blockade and Sphingosine-1-phosphate activation facilitate engraftment of haematopoietic stem and progenitor cells in a non-myeloablative transplant model. Br J Haematol. doi: 10.1111/bjh.12641. [Epub ahead of print]

de Oliveira-Carlos V, Ganz J, Hans S, Kaslin J, Brand M. (2013).  Notch receptor expression in neurogenic regions of the adult zebrafish brain. PLoS One. 8(9):e73384. 

Kyritsis N, Kizil C, Brand M. (2013). Neuroinflammation and central nervous system regeneration in vertebrates. Trends Cell Biol., doi:pii: S0962-8924(13)00137-2. 10.1016/j.tcb.2013.08.004.

Meziane H, Fraulob V, Riet F, Krezel W, Selloum M, Geffarth M, Acampora D, Hérault Y, Simeone A, Brand M, Dollé P, Rhinn M. (2013).  The homeodomain factor Gbx1 is required for locomotion and cell specification in the dorsal spinal cord. PeerJ. 1:e142. 

Kizil C, Iltzsche A, Kaslin J, Brand M. (2013).  Micromanipulation of gene expression in the adult zebrafish brain using cerebroventricular microinjection of morpholino oligonucleotides. J Vis Exp. (75):e50415. 

Jászai J, Graupner S, Tanaka EM, Funk RH, Huttner WB, Brand M, Corbeil D. (2013). Spatial distribution of prominin-1 (CD133)-positive cells within germinative zones of the vertebrate brain. PLoS One. 8(5):e63457. 

Bökel C, Brand M. (2013).  Generation and interpretation of FGF morphogen gradients in vertebrates. Curr Opin Genet Dev. 23(4):415-22. 

Jungke P, Hans S, Brand M. (2013).  The zebrafish CreZoo: an easy-to-handle database for novel CreER(T2)-driver lines. Zebrafish. 10(3):259-63.

Kaslin J, Kroehne V, Benato F, Argenton F, Brand M. (2013).  Development and specification of cerebellar stem and progenitor cells in zebrafish: from embryo to adult. Neural Dev. 8:9.

Hans S, Irmscher A, Brand M. (2013).  Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage. Development. 140(9):1936-45.

Müller P, Rogers KW, Yu SR, Brand M, Schier AF. (2013).  Morphogen transport. Development. 140(8):1621-38. 

Grandel H, Brand M. (2013).  Comparative aspects of adult neural stem cell activity in vertebrates. Dev Genes Evol. 223(1-2):131-47.

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. 

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. Science338(6112):1353-6 

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. 23(6):1230-7

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. 

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. 

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(22):4831-41

Nowak, M., Yu, Shuizi Rachel, Gupta, Mansi, Machate, Anja and Brand, Michae (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 B, Doitsidou M, Tarbashevich K, Laguri C, Yu SR, Ries J, Dumstrei K, Thelen S, Dörries J, Messerschmidt EM, Thelen M, Schwille P, Brand M, Lortat-Jacob H, Raz E.(2011) Cxcl12 evolution--subfunctionalization of a ligand through altered interaction with the chemokine receptor.Development.138(14):2909-14.

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. 

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. 

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. 

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

                    

 updated: 23.7.13

Last Modified: 26/05/2016