We study the development of the vertebrate nervous system and the musculature. Our main goals are to understand the gene networks controlling differentiation and function of the nervous system and musculature, and how these processes are disturbed by environmental toxins. We use genetic, embryological. biochemical and cell biological methods to unravel the underlying regulatory processes. As experimental systems, we employ mostly zebrafish but also mouse.

Cell-cell communication and signal integration

Cross-talk between cells by secretion of signaling molecules is essential for development and body homeostasis. Disturbance of these processes leads to malformations and disease including cancer. The cis-regulatory elements of downstream genes are integration points, at which these signals converge. A major emphasis of our work is the elucidation and functional characterization of the cis-regulatory elements that control several key genes in neural development. These include the secreted protein sonic hedgehog and the transcription factor neurogenin1. Several of the regulatory sequences under investigation are conserved between zebrafish and mammalian gene homologues suggesting that the mechanisms controlling the expression of these genes were maintained during vertebrate evolution. The ultimate aim of this work is to decipher the regulatory code that controls expression in the developing nervous system of vertebrates.

Genetics of nervous system and muscle development and maintenance

Motility develops very early in the zebrafish embryo offering a fast assay in screens to identify mutations in genes involved in the development and function of the embryonic nervous system. We carried out such F3 screens previously and are in the process to clone the affected genes. These zebrafish mutants mimic inheritable myopathies and neuropathies of humans. They serve therefore as important models to investigate the molecular mechanisms underlying the corresponding human pathologies.

Development is driven by the controlled differentiation of embryonic stem cells. Stem cells play also crucial roles in the maintenance of tissues in the adult organism. We are interested to elucidate and compare the mechanisms of stem cell maintenance and differentiation in the muscle and nervous system of the embryo and the adult. Zebrafish are well suited for such a research interest as they show even in the adult central nervous system a remarkable ability to regenerate.

The zebrafish embryo as a model for molecular toxicology

We are exposed to a steadily increasing number of different chemicals. A central issue for human health protection is the development of efficient animal models to monitor and to predict the toxic affect of existing and novel compounds. Our aim is to develop the zebrafish as animal model for molecular toxicology. We use microarray technology, transgenesis and genetics to unravel the molecular pathways affected by model toxins. We focus on toxins that affect neural and muscular development. We believe that this work will elucidate the molecular mechanism of toxicity and help to predict the toxicity of novel compounds.