Drosophila Segment Polarity Mutants and the Rediscovery of the Hedgehog Pathway Genes

The Nüsslein-Volhard and Wieschaus screen for mutations disrupting the segmentation of the Drosophila embryo revolutionized developmental genetics, leading the way to the identification of many of the transcription factors and signaling pathways that orchestrate development, not just in the fruit fly but across the animal kingdom. The Hedgehog signaling pathway is a case in point: yet remarkably, all but one of the genes encoding the Hedgehog pathway components-including Hedgehog itself-had previously been discovered, in some cases decades earlier. Here I review the original identification of these genes and consider why their significance remained obscure until the Nobel Prize winning screen.