CrebA regulates secretory activity in theDrosophilasalivary gland and epidermis

Abstract

Understanding how organs acquire the capacity to perform their respective functions is important for both cell and developmental biology. Here, we have examined the role of early-expressed transcription factors in activating genes crucial for secretory function in the Drosophila salivary gland. We show that expression of genes encoding proteins required for ER targeting and translocation, and proteins that mediate transport between the ER and Golgi is very high in the early salivary gland. This high level expression requires two early salivary gland transcription factors; CrebA is required throughout embryogenesis and Fkh is required only during late embryonic stages. As Fkh is required to maintain late CrebA expression in the salivary gland, Fkh probably works through CrebA to affect secretory pathway gene expression. In support of these regulatory interactions, we show that CrebA is important for elevated secretion in the salivary gland. Additionally, CrebA is required for the expression of the secretory pathway genes in the embryonic epidermis, where CrebA had previously been shown to be essential for cuticle development. We show that zygotic mutations in several individual secretory pathway genes result in larval cuticle phenotypes nearly identical to those of CrebA mutants. Thus, CrebA activity is linked to secretory function in multiple tissues.

Epithelial-to-Mesenchymal Transition Activates PERK–eIF2α and Sensitizes Cells to Endoplasmic Reticulum Stress

“…Secretory cells often upregulate ER protein-folding and transport capacity to sustain their increased output ( 28,29 ). Consistent with this, expression of 18 genes critically involved in secretory pathway components (SPCG; ref.…”

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

“…We used a set of highconfidence direct CrebA targets 107 and three genome-wide chromatin confidence levels select for motif instances in regions they are known to be functional: conserved transcription factor (TF) motifs enrich for promoters; miRNA motifs for 39UTRs, and specifically the transcribed strand. Regions are normalized for their overall length, measured by the number of motif instances without conservation (0% confidence baseline).…”

A Targeted Gain-of-Function Screen Identifies Genes Affecting Salivary Gland Morphogenesis/Tubulogenesis in Drosophila

“…In the absence of Fkh, invagination fails completely (Myat and Andrew 2000a). Several direct targets of Fkh have been identified, including the transcription factors senseless (Chandrasekaran and Beckendorf 2003) and sage (Abrams et al 2006); PH4aSG2, a prolyl-4-hydroxylase (Abrams et al 2006); and crebA, which in turns control the expression of secretory genes in the glands (Abrams and Andrew 2005).…”

“…The genes affected could be classified according to their predicted function (see Table 1). Several of the genes identified by positive insertions have previously been implicated in salivary gland morphogenesis or function within the glands: chickadee (Chandrasekaran and Beckendorf 2005), tec29 (Chandrasekaran and Beckendorf 2005), doughnut on 2 (Harris and Beckendorf 2007), rhomboid1 and spitz (Kuo et al 1996), tapd (Abrams and Andrew 2005), and slit (Kolesnikov and Beckendorf 2005). Three of the insertions identifying these could potentially induce antisense RNA expression and could thus mimic a loss-of-function situation (chic, tec29, slit), and three insertions could induce overexpression (dnt, rhomboid1, spitz).…”