C.H.S.-Stiftung

zur Förderung biomedizinischer Forschung

 

 

Dr. Catherina G. Becker

1993             PhD Neurobiology with honours, University of Bremen

1994-1996    Postdoc, Swiss Federal Institute of Technology, Zürich

1996-1998    Postdoc, Dept Dev Cell Biol, University of California, Irvine

1998-2000    Postdoc, Centre for Molecular Neurobiology Hamburg (ZMNH)

2000-2005    Group Leader, Centre for Molecular Neurobiology Hamburg (ZMNH)

2005             Senior Lecturer, Division of Veterinary Biomedical Sciences,

                     University of Edinburgh

 

Dr. Becker was a recipient of a C.H.S. Stiftung Short Term Fellowship from 01.01.2005 to 31.03.2005.

 

 

Research:

 

Axon tracts in the central nervous system (CNS) are not repaired in man, leading to permanent paralysis after spinal cord injury. In contrast to mammals, adult fish are capable of regenerating axonal connections and even to regenerate CNS tissue from adult progenitor cells. We are using the adult zebrafish to study successful regeneration of axonal connections in the CNS, since this model organism offers the unique opportunity to analyse axon growth both during early vertebrate development and during axon regeneration in the adult central nervous system. Embryos are transparent and their relatively simple scaffold of primary axons has been described in detail. The availability of mutant zebrafish, DNA micro-arrays for expression profiling, expressed sequence tags and sequencing of the zebrafish genome, which is projected to be complete this year, provide easy access to genes of interest and new methods to perturb gene function are being devised for this important model organism.

 

We are specifically interested in how a growth state in the injured neurons is re-initiated and how regenerating axons are capable of navigating a complex adult CNS environment to precisely reinnervate their former targets. We argue that molecules which have functions for developmental axon growth and pathfinding are likely to play a role in axon regeneration as well. We have shown that developmentally expressed cell recognition molecules, such as the L1- related L1.1, are reexpressed by neurons with regenerating axons and are functionally important for spinal cord regeneration. We could also show that molecules of the extracellular matrix, such as chondroitin sulfate proteoglycans and tenascins are repellent guidance cues for developing and regenerating optic axons, suggesting that also regenerating axons negotiate their path by interacting with local molecular cues. We are now using expression profiling to identify transcription factors and guidance receptors that are upregulated during regeneration. To analyze the functions of these molecules for axon growth we localize the molecules by in situ hybridisation and immunohistochemistry both in embryos and during adult regeneration. Functional analyses use micro-injection of anti-sense oligonucleotides (morpholinos) for knock down and RNA and DNA injection for overexpression experiments. Available mutants are analysed during axonal regeneration. Using these approaches in the zebrafish we hope to gain insight into general developmental processes and at the same time into the factors necessary for repair of the central nervous system after injury.

 

Selected Publications:

 

Becker CG, Becker T, (eds) Model organisms in central nervous system regeneration, Wiley-VCH, Weinheim, 2006.

Schweitzer J, Becker T, Schachner M, Becker CG (2005).
Expression of collapsin response mediator proteins in the nervous system of embryonic zebrafish correlates with neuronal differentiation, Gene Expr. Patterns, in press supported by the C.H.S. Stiftung.

Lieberoth B, Becker CG, Schachner M, Becker T (2005).
Intraspinal neurons with an axon ascending to the brain lack the capacity to regenerate in adult zebrafish, Mol Cell Neurosci, in press

Becker CG, Schweitzer J, Feldner J, Schachner M, Becker T (2004).
Tenascin-R as a repellent guidance molecule for newly growing and regenerating optic axons in adult zebrafish, Mol Cell Neurosci 26:376-389.

Becker CG, Lieberoth BC, Morellini F, Feldner J, Becker T, Schachner M (2004).
L1.1 is involved in spinal cord regeneration in adult zebrafish, J Neurosci 24:7837-7842, with editorial coverage.

Becker T, McLane MA, Becker CG (2003).
Integrins function in growth and pathfinding of ventral motor nerves in the trunk of embryonic zebrafish, Molec. Cell. Neurosci. 23:54-68 (Cover).

Becker CG, Schweitzer J, Feldner J, Becker T, Schachner M (2003).
Tenascin-R as a repellent guidance molecule for developing optic axons in zebrafish, J Neurosci 23(15):6232-6237.

Becker CG, Becker T (2002).
Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. J Neurosci 22:842-853.

Becker T, Becker CG (2001)
Regenerating descending axons preferentially reroute to the grey matter in the presence of a general microglial/macrophage reaction caudal to a spinal transection in adult zebrafish. J Comp Neurol 433:131-147.

Becker CG, Meyer RL, Becker T (2000)
Gradients of ephrin-A2 and ephrin-A5b mRNA during retinotopic regeneration of the optic projection in adult zebrafish. J. Comp. Neurol. 427(3):469-483.

Becker CG, Becker T, Meyer RL, Schachner M (1999)
Tenascin-R inhibits the growth of optic fibers in vitro but is rapidly eliminated during nerve regeneration in the salamander Pleurodeles waltl. J. Neurosci 19:813-827.

 

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