The bHLH protein, Sage, provides tissue specificity to FoxA/Fork head. Rebecca M. Fox, Aria Vaishnavi, Rika Maruyama, Deborah J. Andrew. Dept Cell Biol, Johns Hopkins Univ, Baltimore, MD.
Tissue morphogenesis is coordinated by the actions of transcription factors. In the salivary gland (SG), the homeotic genes Sex combs reduced (Scr), homothorax (hth), and extradenticle (exd) initiate SG specification by activating expression of the transcription factors Fork head (Fkh), Sage, CrebA and Huckebein (Hkb). Fkh is required for SG invagination as well as for maintaining its own expression and expression of many other SG genes. CrebA regulates the high-level secretory capacity required for SG function, and Hkb is required for SG tube elongation. Sage is the only SG specific transcription factor and has been implicated in the maintenance of the SG lumen through its regulation of two prolyl-4 hydroxylase genes, PH4SG1 and PH4SG2. We have generated Sage null mutants and discovered that Sage is required for SG survival in late embryos. To identify Sage target genes, we performed microarray analyses and discovered that Sage regulates genes encoding proteins secreted from the SG and the enzymes that modify these secreted products. Interestingly, whereas overexpression of either Fkh or Sage alone is not sufficient to induce ectopic SG target gene expression, coexpression of Fkh and Sage can activate SG gene expression in multiple ectopic locations. Consistent with this finding, we have discovered that Sage and Fkh protein localize to the same sites on SG polytene chromosomes, indicating that the two proteins act directly on the same sets of target genes. Thus, we have identified a SG specific transcripton factor, Sage, that functions with the FoxA factor, Fkh, to activate SG specific gene expression. These findings suggest a paradigm wherein a bHLH factor with very limited expression acts with the more widely expressed FoxA transcription factor to provide tissue specificity.