The xbp-1 gene is essential for development in Drosophila

Abstract

We report in this paper the characterization of Dxbp-1, the Drosophila homologue of the xpb-1 gene that encodes a "bZIP"-containing transcription factor that plays a key role in the unfolded protein response (UPR), an evolutionarily conserved signalling pathway activated by an overload of misfolded proteins in the endoplasmic reticulum (ER). Dxbp-1 is ubiquitously transcribed, and high levels are found in embryonic salivary glands and in the ovarian follicle cells committed to the synthesis of the respiratory appendages. Loss of function of Dxbp-1 induced a recessive larval lethality, thus, revealing an essential requirement for this gene. The Dxbp-1 transcript was submitted to an "unconventional" splicing that generated a processed Dxbp-1s transcript encoding a DXbp-1 protein isoform, as is the case for yeast, Caenorhabditis elegans and vertebrate hac1/xbp-1 transcripts after UPR activation. However, in the absence of exogenously induced ER stress, the Dxbp-1s transcript was also detectable not only throughout embryonic and larval development but also in adults with a high level of accumulation in the male sexual apparatus and, to a lesser extent, in the salivary glands of the third-instar larvae. Using a Dxbp-1:GFP transgene as an in vivo reporter for Dxbp-1 mRNA unconventional splicing, we confirmed that Dxbp-1 processing took place in the salivary glands of the third-instar larvae. The Dxbp-1 gene appears, thus, to play an essential role during the development of Drosophila, hypothetically by stimulating the folding capacities of the ER in cells committed to intense secretory activities.