Development and Regeneration of the Vertebrate Brain
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.
In contrast to mammals, the central nervous system (CNS) of adult zebrafish retains an amazing number of active neural stem 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 stem cell recruitment during normal homeostasis and in the context of regeneration.
Using various CNS lesion paradigms, transgenesis, Cre/loxP technology and next generation sequencing we ask, for instance, which genes and pathways regulate adult neural stem cell activity and their ability to repair damage. Additionally, 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 how CNS regeneration can be stimulated also in mammalian brains and pave the way for stem cell based regenerative therapies.
Future Projects and Goals
- Identification of the molecular mechanisms that allow adult CNS regeneration in a regeneration-capable organism to rekindle regeneration also in the mammalian CNS
- organizer-dependent patterning in the embryonic and adult vertebrate brain
Methodological and Technical Expertise
- zebrafish genetics and genomics
- site-specific recombinase technology (Cre/lox)
- cerebroventricular microinjection (CVMI)
- Fluorescence Correlation Spectroscopy (FCS)
Yu SR, Burkhardt M, Nowak M, Ries J, Petrásek Z, Scholpp S, Schwille P, Brand M.
Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.
Nature 461:533-6. (2009)
Nowak M, Yu SR, Gupta M, Machate A. Brand M
Interpretation of the Fgf8 morphogen gradient is regulated by endocytic trafficking.
Nature Cell Biology 13(2):153-8. (2011)
Hochmann S, Kaslin J, Hans S, Weber A, Machate A, Geffarth M, Funk R. H. W., Brand M.
Fgf Signaling is Required for Photoreceptor Maintenance in the Adult Zebrafish Retina.
PLoS ONE 7(1): e30365. (2012)
Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M.
Acute Inflammation Initiates the Regenerative Response in the Adult Zebrafish Brain.
Science, 338(6112):1353-6. (2012)
Kizil C, Kyritsis N, Dudczig S, Kroehne V, Freudenreich D, Kaslin J, Brand M.
Regenerative neurogenesis from neural progenitor cells requires injury-induced expression of Gata3.
Developmental Cell, 23(6):1230-7. (2012)