THE CELL-SURFACE METALLOPROTEASE DISINTEGRIN KUZBANIAN IS REQUIRED FOR AXONAL EXTENSION IN DROSOPHILA

It has long been suspected that proteolytic activity associated with a dvancing growth cones may be required for axon extension. We have isol ated mutations in the kuzbanian (kuz) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disi ntegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloproteas e is required for axon extension, suggesting a requirement for proteol ytic activity at the growth cone surface.