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The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases plays important roles in animal development and pathogenesis. However, transcriptional regulation of ADAMTS proteins during development remains largely unexplored. Here we show that basic helix–loop–helix (bHLH) transcription factors regulate the expression of an ADAMTS protease that is required for gonad development in
Caenorhabditis elegans. Mutations in the gene
mig-24 cause shortened and swollen gonad arms due to a defect in gonadal leader cell migration, although leader cell specification appears to occur normally. The MIG-24 protein is a bHLH transcription factor of the Achaete–Scute family and is specifically expressed in gonadal leader cells. MIG-24 can physically interact with HLH-2, an E/Daughterless family bHLH transcription factor and bind the promoter region of
gon-1, which encodes an ADAMTS protease required for gonadal leader cell migration. Mutations or RNA interference of
mig-24 and
hlh-2 severely impaired
gon-1 expression and forced expression of GON-1 in leader cells in
mig-24 mutants partially rescued the gonadal elongation defect. We propose that, unlike most previously characterized Achaete–Scute transcription factors that are involved in cell fate specification, MIG-24 acts with HLH-2 in specified cells to control cell migration by activating the expression of the GON-1 ADAMTS protease.