With Wolfgang Driever, published in Cell that Bicoid protein determines embryonic position in a concentration-dependent manner — the first morphogen shown experimentally.
On 1 July 1988, Nüsslein-Volhard and her colleague Wolfgang Driever published the paper "The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner" in the journal Cell.
This publication provided the first direct experimental demonstration of a morphogen gradient — a concept theorized decades earlier by Lewis Wolpert but never conclusively shown in a living organism. Nüsslein-Volhard and Driever proved that the Bicoid protein forms a concentration gradient from the anterior to the posterior of the fruit fly embryo, and that the local concentration of this single protein instructs cells about their position along the body axis, directly activating different target genes at different threshold concentrations.
This was a foundational discovery in developmental biology, providing a molecular mechanism for how a single fertilized egg can generate a precisely patterned, complex multicellular organism. The bicoid morphogen model became a textbook paradigm cited in biology curricula worldwide and directly influenced research into human developmental disorders, limb formation, and neural patterning. It was among the key discoveries specifically cited by the Nobel Committee when awarding Nüsslein-Volhard the 1995 Nobel Prize in Physiology or Medicine.