Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA

Development. 2013 May;140(10):2160-71. doi: 10.1242/dev.092924. Epub 2013 Apr 11.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Chromosomes / ultrastructure
  • Crosses, Genetic
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Forkhead Transcription Factors
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • RNA-Binding Proteins / metabolism*
  • Salivary Glands / metabolism
  • Salivary Proteins and Peptides / genetics
  • Salivary Proteins and Peptides / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Forkhead Transcription Factors
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Sage protein, Drosophila
  • Salivary Proteins and Peptides
  • Transcription Factors
  • fkh protein, Drosophila
  • sens protein, Drosophila