2002 Balzan Prize for Developmental Biology
Walter Gehring (*1939 – †2014) is a pioneer in the field of molecular developmental biology. His discovery of the Homeobox has opened a new avenue of research that has shed light on the long-standing problem in embryology of how the body plan of multicellular organisms is laid down in the course of embryogenesis.
He studied with the Swiss geneticist Ernst Hadorn in Zurich, and did most of his research on the Drosophila fly. As he was working on his doctorate, he isolated a new mutation in Drosophila causing the transformation of the antennae into legs, a mutation which is called Antennapedia. For the next 30 years this mutant was at the centre of his scientific interests. Other genes whose mutation produces homeotic transformations were discovered and analysed by Edward Lewis in the United States using classical genetic techniques. When the methods of gene technology became available, Gehring cloned the Antennapedia gene. Several other homeotic genes were then cloned by Gehring’s and other groups. The ingenious scientist Walter Gehring then discovered (independently from Matthew Scott’s group in the USA) that all homeotic genes have a 180 base pair sequence in common that he called the Homeobox.
With Eddy De Robertis, he was the first to demonstrate the evolutionary conservation of Homeobox-containing genes present in all metazoan Bilateria, where they play a key role in patterning the body plan. Later on, with Kurt Wüthrich, he determined the three-dimensional structure of the protein domain (called Homeodomain) encoded by the Homeobox at atomic resolution.
He showed that the Homeodomain binds to specific DNA sequences of the promoter region of certain genes. This allows to conclude that Homeobox-containing genes are coding for transcription factors which regulate the activity of other genes. On this basis, Homeobox-containing genes are called developmental control genes.
Walter Gehring made a second discovery of fundamental importance in developmental biology as he identified the Pax6 gene (which contains a Homeobox as well), a “master control gene” for eye development in all animals, including humans. The transcription factor of the Pax6 gene is critical for the development of the eye in all organisms endowed with a visual system.
Mutants with a loss of the function of Pax6 (or its homologues Eyeless in Drosophila, Small eye in mouse, Aniridia in human) prevent eye development at early stages. In 1995, Walter Gehring demonstrated the importance of Pax6 in an elegant experiment in which targeted ectopic expression of this gene in the fly generated eyes on legs, wings or antennae. Moreover, the conservation of this genetic control of eye development throughout evolution was demonstrated by the fact that insect and mammalian genes are interchangeable.
These experiments have opened up the field of evolutionary developmental biology and illustrated a spectacular case of evolution in which similar genetic networks have led to a number of morphologically different visual systems. These findings solve an old problem in evolutionary biology.
The far-reaching implications of Dr. Walter Gehring’s work amply justify his being chosen this year as the Balzan Prize winner in the field of Developmental Biology.