ZFIN ID: ZDB-PERS-000111-1
Roth, Lukas
Email: lukas.w.a.roth@gmx.net
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Affiliation:
Address: (Last known address) Department of Anatomy and Developmental Biology University College London Gower Street London, WC1E 6BT USA
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Phone: Unavailable
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BIOGRAPHY AND RESEARCH INTERESTS
In the work I did in Eva Reinhard's lab (Biozentrum, Basel, Switzerland), I focused on the characterization of the molecular machinery underlying the regeneration of the central nervous system (CNS). We isolated and analyzed several genes that were previously unknown or not reported to be associated with neuronal repair. Part of my work involved the characterization of beta-thymosin, an actin-monomer binding protein. During development as well as regeneration, beta-thymosin is expressed in a subset of growing neurons and in glia cells along their axon tracts. Experiments inhibiting beta-thymosin function during embryonic development demonstrated that the gene is essential for tract formation. These results highlight the importance of actin cytoskeleton modulations during regeneration and development of the nervous system. Furthermore, we found that all of the identified genes are coordinately regulated in the regrowing CNS despite having different functions, suggesting a conserved activation mechanism. This mechanism seems to be regeneration specific as the same genes are expressed individually during the development of the nervous system.

At UCL I worked on cytoskeletal rearrangements and boundary formation in the zebrafish hindbrain. During segmentation of the vertebrate hindbrain, a series of tissue constrictions demarcate the forming rhombomeres. Once the boundaries have formed, there is a restriction in cell migration between rhombomeres. Studies on Eph receptors and ephrins have shown that both are involved in the formation of boundaries between segments, in somites as well as in the hindbrain. Whereas many of the genes involved in patterning are described, the mechanisms by which boundaries actually arise are not known. Based on preliminary results, we hypothesized that an interaction between Eph receptors and ephrins at the interface of their expression domains lead to a modulation of the actin cytoskeleton to create a boundary there. The aim of my project was to elucidate the boundary formation process in the zebrafish hindbrain and to investigate the interaction of the Eph receptors and their ligands triggering this process. To this end, I generated several lines of fish expressing a GFP-actin fusion protein which others in the group are currently analysing. I also helped characterise a new mutant line we called wingnut because of the odd shape of its optic primordia. For more information see the genetic screens section of the lab's research pages (http://www.ucl.ac.uk/zebrafish-group/).

***I now work as a computational biologist (bioinformatics) in industry where I'm involved in expression profiling, data mining and drug target discovery. If you want to know more about my past or present work contact me via email.***


PUBLICATIONS
Cooke, J.E., Moens, C.B., Roth, L.W., Durbin, L., Shiomi, K., Brennan, C., Kimmel, C.B., Wilson, S.W., and Holder, N. (2001) Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development (Cambridge, England). 128(4):571-580
Roth, L.W.A., Bormann, P., Widerkehr, C., and Reinhard, E. (1999) β-Thymosin, a modulator of the actin cytoskeleton is increased in regenerating retinal ganglion cells. The European journal of neuroscience. 11(10):3488-3498
Roth, L.W., Bormann, P., Bonnet, A., and Reinhard, E. (1999) ß-thymosin is required for axonal tract formation in developing zebrafish brain. Development (Cambridge, England). 126(7):1365-1374
Bormann, P., Roth, L.W., Andel, D., Ackermann, M., and Reinhard, E. (1999) zfNLRR, a novel leucine-rich repeat protein is preferentially expressed during regeneration in zebrafish. Molecular and cellular neurosciences. 13(3):167-179
Bormann, P., Zumsteg, V.M., Roth, L.W.A., and Reinhard, E. (1998) Target contact regulates GAP-43 and alpha-tubulin mRNA levels in regenerating retinal ganglion cells. Journal of neuroscience research. 52:405-419

NON-ZEBRAFISH PUBLICATIONS