About Dr Silke Rinkwitz
Zebrafish is used as a vertebrate model system to study genes that have critical roles for the development of the brain. We create transgenic zebrafish with the goal to label neuronal subtypes, which express fluorescent markers under control of individual gene regulatory sequences that were predicted by bioinformatics. The identification of the critical enhancers is used as a tool for partitioning of gene expression patterns and further to detect formerly unknown sites of activity of the gene. To investigate neuronal migration or axonal pathfinding, the identified regulatory sequences can then be used in functional studies to reveal the anatomy of the neurons and to manipulate the activity of the gene. We are currently expanding this approach to the regulation of micro RNAs, where we identify micro RNA promoters and -enhancers and use these sequences to define patterns of micro RNA activity in the brain and to functionally modify the cells that express them.
A major focus of our zebrafish work was on Hox genes, which are key regulators of anterior-posterior axis patterning and have a major role in hindbrain development. With the goal to label neuronal subtypes that express Hox3 and Hox4 genes in the developing posterior hindbrain, we identified cis-regulatory sequences of these genes that are able to control specific neuronal expression in zebrafish transgenes. Putative enhancers were identified by comparative genomic alignments and then tested in reporter gene constructs (Hadrys et al. 2004; Hadrys et al., 2006 and Punnamoottil et al, in revision). YFP transgenic larvae expressing YFP under Hox4 (i. e. hoxa4a, hoxb4a and hoxd4a genes) regulatory control that resulted from a large-scale enhancer trap screen revealed the hindbrain neuronal subtypes in which the Hox4 genes are active (Punnamoottil et al., 2008). About 300 further YFP transgenic zebrafish lines resulting from enhancer trap insertions into the zebrafish genome were characterized for their expression patterns and for the gene content at the site of integration as well as for gene regulatory mechanisms and genomic architecture.
<!--StartFragment--> Silke Rinkwitz (SR) was educated in mouse developmental genetics and analysed the expression of homeobox genes in the developing hypothalamus in Germany. She proceeded in developmental genetics during her PhD thesis by analysing the function of homeobox genes in mouse and chick inner ear development. During two years of postdoctoral research at NYU Medical School in the USA, she started to work on hindbrain development using the zebrafish. At the end of 2002, she was appointed as assistant professor in Neurogenetics (Oldenburg University, Germany), a position with commitment for undergraduate and graduate level teaching. She established a research group and started work in comparative genomics and cis-regulation with focus on Hox genes in hindbrain development. Her lab was among the first labs that analysed larger genomic regions for sequence conservation with the goal to identify conserved non-coding elements and to test their activity in reporter gene constructs in zebrafish. In 2006 she joined the lab of Thomas Becker at Sars Centre (Bergen, Norway) and now at Brain and Mind Research Institute at the University of Sydney. She currently has several projects that aim to test enhancers on a large scale in stable GFP transgenesis and analysed data resulting from more than 300 insertions into the zebrafish genome, which she coordinates with the Sanger Institute zebrafish genome group. <!--EndFragment-->