Abrams Elliott W, Andrew Deborah J
Department of Cell Biology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Development. 2005 Jun;132(12):2743-58. doi: 10.1242/dev.01863. Epub 2005 May 18.
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.
了解器官如何获得执行其各自功能的能力对于细胞生物学和发育生物学都很重要。在这里,我们研究了早期表达的转录因子在激活果蝇唾液腺分泌功能关键基因中的作用。我们发现,编码内质网靶向和转运所需蛋白质以及介导内质网与高尔基体之间运输的蛋白质的基因在早期唾液腺中的表达非常高。这种高水平表达需要两种早期唾液腺转录因子;整个胚胎发育过程都需要CrebA,而Fkh仅在胚胎后期阶段需要。由于Fkh是维持唾液腺后期CrebA表达所必需的,Fkh可能通过CrebA起作用来影响分泌途径基因的表达。为支持这些调控相互作用,我们表明CrebA对唾液腺中分泌增加很重要。此外,胚胎表皮中分泌途径基因的表达需要CrebA,此前已证明CrebA对表皮发育至关重要。我们发现几个单个分泌途径基因的合子突变导致幼虫表皮表型与CrebA突变体的表型几乎相同。因此,CrebA的活性与多个组织中的分泌功能相关。