Vallee Visiting Professor Lecture by Prof. Walter Gehring, Biozentrum, University of Basel, Switzerland
Homeobox genes in development and evolution
The Homeobox story begins with the discovery of a homeotic mutation in Drosophila, which transforms the antennae on the head of the fly into middle legs. When gene cloning methods were developed, this gene was cloned and it was found to contain a sequence of 180 basepairs which it shares with numerous other homeotic genes and was designated as the homeobox. It encodes a DNA binding domain of 60 aminoacids called the homeodomain, which is highly conserved in evolution and was found in all metazoa, including humans. A gene family designated as Hox genes, which specifies the body plan is arranged in the same order on the chromosomes as the genes are expressed along the antero-posterior axis to specify the the body segments, in flies, mice and humans. This reveals for the first time a general universal principle underlying animal development.
In collaboration with Kurt Wüthrich we have determined the molecular structure of the homeodomain at atomic resolution by NMR spectroscopy and confirmed the structure determination by genetic experiments. Single molecule imaging studies in collaboration with Rudolf Rigler at the Karolinska Institute allowed us to find out how the homeodomain transcription factors find their target genes in the living cell.