title: Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.
abstract: FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205-2196, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Fox
authors.forename: Aria
authors.initials: A
authors.lastname: Vaishnavi
authors.forename: Rika
authors.initials: R
authors.lastname: Maruyama
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Andrew
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000648:ultrastructure; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012471:Salivary Proteins and Peptides; D014157:Transcription Factors; C479570:Sage protein, Drosophila; C512745:fkh protein, Drosophila; C413162:sens protein, Drosophila