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WIREs Dev Biol
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Building and specializing epithelial tubular organs: the Drosophila salivary gland as a model system for revealing how epithelial organs are specified, form and specialize

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The past two decades have witnessed incredible progress toward understanding the genetic and cellular mechanisms of organogenesis. Among the organs that have provided key insight into how patterning information is integrated to specify and build functional body parts is the Drosophila salivary gland, a relatively simple epithelial organ specialized for the synthesis and secretion of high levels of protein. Here, we discuss what the past couple of decades of research have revealed about organ specification, development, specialization, and death, and what general principles emerge from these studies. WIREs Dev Biol 2014, 3:281–300. doi: 10.1002/wdev.140 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Early Embryonic Development > Development to the Basic Body Plan Invertebrate Organogenesis > Flies
Confocal images of the embryonic salivary gland (SG). (a) Ventral views of the SG stained with nuclear markers. The secretory portion of the SG forms from two placodes of cells on the surface of the embryo, with the duct precursors located between the two secretory placodes (st 10). At this stage, the expression of duct (red) versus secretory (green) markers is not so clear. During st 11, the gland invaginates into the embryo. At this stage, the distinction between duct (red) and secretory markers (green) is more evident. As development progresses (st 12–15), the secretory tubes elongate, and the individual duct (id) and common ducts (cd) form. (b) Lateral views of SG during elongation and migration. All membranes are marked in green, with the apical membrane specifically marked in red. Following invagination, the SG moves dorsally (st 11) and then turns (st 12) and migrates posteriorly. Posterior migration continues (st 14–16) until the SG reaches its final resting place. Throughout this dynamic process, the SG migrates as an intact fully polarized tissue.
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Fkh (likely in collaboration with Sage and Sens) keeps the salivary gland (SG) alive until the prepupal stage by preventing expression of the apoptosis inducers reaper (rpr) and head involution defective (hid). Fkh (and Sage +/− Sens) in combination with low level ecdysone signaling activate transcription of the Salivary glue secretion (Sgs) genes in late larvae. High‐level ecdysone signaling just prior to pupation activates expression of the early ecdysone‐responsive genes, which encode transcription factors. A subset of these transcription factors repress fkh and Sgs transcription and activate expression of genes required for glue secretion. Thus, the glue is secreted when Fkh begins to disappear. In turn, the disappearance of Fkh results in rpr and hid expression, which overcome DIAP and activate the cell death pathway. Thus, the SG dies shortly after it completes its final task of glue secretion.
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Confocal image of the larval salivary gland with the different cell types artificially colorized. The larval salivary gland includes the large polytenized secretory cells (light blue), the medium sized duct cells (light purple) and the small imaginal ring cells (blue). The fat body (green) attaches to the secretory cells at several places.
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The salivary gland (SG) contacts or comes close to several tissues as it migrates to its correct final position in the embryo, including the circular (c) visceral mesoderm (cVM), the longitudinal (l) visceral mesoderm (lVM), the fat body, the somatic musculature and the CNS. The cVM provides a suitable substrate for posterior SG migration through the expression of αPS2βPS integrin that binds a secreted laminin also expressed in the cVM. The SG expresses αPS1βPS integrin, which also binds the secreted laminin. Both the integrins and laminin are essential for posterior migration (starred). The lVM migrates between the SG and the cVM to detach these two cell types. The SG also expresses several receptor genes, which allow it to properly navigate to its final correct position in response to local sources of the corresponding ligands. In turn, the SG is likely to also provide cues for the migration of other cell types in the embryo. For example, the fat body migrates over specific parts of the SG at late embryonic stages.
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The duct is specified by Scr, Exd, and Hth in combination with EGF signaling. EGF‐signaling blocks expression of Fkh in the most ventral cells of PS2, allowing the expression of duct‐specific genes such as Trh and its downstream targets, btl, eyg and, presumably, other genes. The absence of Fkh expression in the ventral cells also allows expression of two other duct‐specific factors: Dri and Ser. Ser in duct cells is important for establishing the imaginal ring cell fate.
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The secretory specific genes directly activated by Scr, Exd, and Hth include several transcription factors—CrebA, Fork head (Fkh), Sage and Huckebein—as well as a splicing factor—Pasilla. The early expressed genes both maintain and implement the secretory cell fate decision. Pasilla and CrebA function to increase secretory capacity in the professional secretory cells of the salivary gland (SG). Fkh maintains its own expression as well as expression of CrebA and Sage. Fkh also controls morphogenesis and in collaboration with Sage and their downstream target Senseless, activates expression of SG‐specific genes and represses the apoptotic genes reaper and hid, keeping the SGs alive. Huckebein mediates tube elongation.
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SGs are specified by the integration of patterning information along both major body axes. Scr (purple in cartoon), a Hox protein expressed in PS2 and dorsal cells of PS3, is the only spatially regulated activator of salivary gland (SG) cell fates. The more globally expressed Exd and Hth Tale‐homeodomain proteins are also required for SG formation and these proteins function at multiple levels. Tsh (brown in cartoon), expressed in PS3‐13, and Abd‐B (red in cartoon), expressed in PS14, block SG activation in the trunk and abdomen. SG formation is limited to the ventral cells of PS2 by Dpp signaling (blue in cartoon) in the dorsal cells. EGF‐signaling (green in cartoon) along the ventral midline specifies the duct cell fate by blocking expression of Fkh. In turn, Fkh plays a major role in maintaining the secretory cell fate by regulating itself as well as multiple other secretory specific genes and by blocking expression of duct‐specific genes. Ser, which is expressed in duct cells, signals adjacent Notch expressing cells in the common secretory/imaginal ring cell primordia to become imaginal ring cells (dark blue in diagram)—the precursors to the adult SG.
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Early Embryonic Development > Development to the Basic Body Plan
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Invertebrate Organogenesis > Flies