Blind spot and Kohtalo, two components of the Drosophila mediator complex, act together to control a subset of Hedgehog and Wingless target genes. F. Janody , A. Benlali , Z. Martirosyan , J. Treisman. Skirball Institute, Dept Cell Biol, NYU School of Medicine, New York, NY.

   Precise regulation of gene expression is critical during development. Distinct sequence-specific transcription factors carry out this regulation by recruiting components of the basal transcriptional machinery. This recruitment often requires an intermediary coactivator such as the Drosophila mediator complex. This multiprotein complex is required for the activity of diverse transcriptional activators in vitro, and some of its subunits interact physically with specific transcription factors. In a screen to identify new genes involved in early Drosophila eye development, we isolated null mutations of the blind spot (bli) and kohtalo (kto) genes, which encode the Drosophila homologs of two subunits of the mediator complex, TRAP240 and TRAP230. Mutations in bli and kto show identical developmental phenotypes and the encoded proteins interact with each other, suggesting that these two subunits of the mediator complex act as a dimer to fulfill the same function. Loss of function of either gene disrupts photoreceptor differentiation and causes defects in the expression of Hedgehog (Hh) target genes in the eye disc. bli or kto mutant clones are also able to cross compartment boundaries in the wing disc, indicating that these genes are required for Hh, Apterous and/or Notch to control cell affinity. Both genes are also essential for activation of Distal-less by Wingless signaling in the wing disc. However, neither gene is necessary for normal cell growth, suggesting that Bli and Kto are not involved globally in transcriptional regulation but may interact directly with specific transcription factors. We are using genetic and biochemical methods to investigate the association of Bli and Kto with such factors, to determine how these proteins could integrate specific input from different signals to regulate developmental gene expression.