ABSTRACTInStreptomyces, the Bld (Bald) regulators control formation of the reproductive aerial hyphae. The functions of some of these regulators have been well characterized, but BldB has remained enigmatic. In addition to thebldBgene itself,Streptomyces venezuelaehas 10 paralogs ofbldBthat sit next to paralogs ofwhiJandabaA. Transcriptome sequencing (RNA-seq) revealed that loss of BldB function causes the dramatic transcriptional upregulation of theabaAparalogs and a novel inhibitor of sporulation,iosA, and that cooverexpression of just two of these genes,iosAandabaA6, was sufficient to recapitulate thebldBmutant phenotype. Further RNA-seq analysis showed that the transcription factor WhiJ9 is required for the activation ofiosAseen in thebldBmutant, and biochemical studies showed that WhiJ9 mediates the activation ofiosAexpression by binding to direct repeats in theiosA-whiJ9intergenic region. BldB and BldB9 hetero-oligomerize, providing a potential link between BldB and theiosA-whiJ9-bldB9locus. This work greatly expands our overall understanding of the global effects of the BldB developmental regulator.IMPORTANCETo reproduce and disperse, the filamentous bacteriumStreptomycesdevelops specialized reproductive structures called aerial hyphae. The formation of these structures is controlled by thebld(bald) genes, many of which encode transcription factors whose functions have been characterized. An exception is BldB, a protein whose biochemical function is unknown. In this study, we gain insight into the global effects of BldB function by examining the genome-wide transcriptional effects of deletingbldB. We identify a small set of genes that are dramatically upregulated in the absence of BldB. We show that their overexpression causes thebldBphenotype and characterize a transcription factor that mediates the upregulation of one of these target genes. Our results provide new insight into how BldB influencesStreptomycesdevelopment.