The Interactive Fly

Genes involved in tissue and organ development

Ectodermal gut- Foregut and hindgut

gut development description

Cross regulation of intercellular gap junction communication and paracrine signaling pathways during organogenesis in Drosophila

The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus)

The putative Na(+)/Cl(-)-dependent neurotransmitter/osmolyte transporter Inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis

Genes influencing foregut and hindgut

Foregut (pharynx, esophagus and proventriculus)

Hindgut (proctodeum)

Gut Development

The ectodermal derivatives of the gut are the stomodeum and the proctodeum. The proctodeum is formed concurrently with germ-band elongation [Images] while formation of the foregut continues later and is associated with head involution. Adult foregut consists of the esophagus, pharynx, crop and the sucking pump or cibarium found at the base of the proboscis. Salivary gland cells, also of ectodermal origin, become part of the forgut and are derived independently from cells immediately behind the cephalic furrow.

The anterior endodermal anlage invaginates during gastrulation (stage 7) [Images] to produce the anterior midgut primordium, while the posterior midgut primordia sink into the embryo during stage 8 and enter the first postblastodermal division during stage 9. The anlagen for the hindgut form a ring encircling the posterior midgut primordia at the posterior pole. The whole of the hindgut is ectodermal in origin, including Malpighian tubules that form close to the junction between hindgut and posterior midgut.

The entire gut is remodeled during metamorphosis from imaginal cells at the base of the salivary glands (foregut), at the junction of the foregut and midgut, and in the hindgut and around the anus. Malpighian tubules are an exception to this remodeling process. Instead, they persist throughout metamorphosis unmodified.

Genes affecting ectodermal portions of the gut

Foregut is determined by the same genes that act in the gnathal (mouth) segments of head. Foregut is really an extention of mandible, maxillary and labial segments and is regulated by genes that are expressed in these segments including spalt, the head gap genes, and the ANTP-complex genes Deformed and Sex combs reduced.

Why is it that labial, the most anteriorly expressed ANTP-C gene, is not involved in foregut determination? The portion of the blastoderm that invaginates to form ectodermal gut derivatives is really ventral-anterior, resulting in the incorporation of cells of the gnathal segments into the forgut. The more dorsal anterior portions, including the pregnathal intercalary segment (expressing labial) form dorsal anterior structures such as the eyes and brain. tailless and forkhead are required for hindgut, including Malpighian tubules and anal plate, while huckebein is required for foregut only.

Cross regulation of intercellular gap junction communication and paracrine signaling pathways during organogenesis in Drosophila

The spatial and temporal coordination of patterning and morphogenesis is often achieved by paracrine morphogen signals or by the direct coupling of cells via gap junctions. How paracrine signals and gap junction communication cooperate to control the coordinated behavior of cells and tissues is mostly unknown. This study found that Hedgehog signaling is required for the expression of wingless and of Delta/Notch target genes in a single row of boundary cells in the foregut-associated proventriculus organ of the Drosophila embryo. These cells coordinate the movement and folding of proventricular cells to generate a multilayered organ. hedgehog and wingless regulate gap junction communication by transcriptionally activating the innexin2 gene, which encodes a member of the innexin family of gap junction proteins. In innexin2 mutants, gap junction-mediated cell-to-cell communication is strongly reduced and the proventricular cell layers fail to fold and invaginate, similarly as in hedgehog or wingless mutants. It was further found that innexin2 is required in a feedback loop for the transcriptional activation of the hedgehog and wingless morphogens and of Delta in the proventriculus primordium. It is proposed that the transcriptional cross regulation of paracrine and gap junction-mediated signaling is essential for organogenesis in Drosophila (Lechner, 2007).

In both vertebrates and invertebrates, the posterior foregut constitutes a center of organogenesis from which gut-associated organs such as the lung in vertebrates or the proventriculus in Drosophila develop. Proventriculus development involves the folding and invagination of epithelial cell layers to generate a multiply-folded organ. Two cell populations, the anterior and the posterior boundary cells, were shown previously to control cell movement and the folding of the proventriculus organ. In the posterior boundary cells, which organize the endoderm rim of the proventriculus, the JAK/STAT signaling cascade cooperates with Notch signaling to control the expression of the gene short stop encoding a cytoskeletal crosslinker protein of the spectraplakin superfamily. Thereby the Notch signaling pathway is connected to cytoskeletal organization in the posterior boundary cells, which have to provide a stiffness function to enable the invagination of the ectodermal foregut cells. The findings in this paper provide evidence that hedgehog is essential for the Notch signaling-dependent allocation of the anterior boundary cells. In amorphic hedgehog mutants, evagination and the formation of the constriction at the ectoderm/endoderm boundary are not affected, however, the inward movement of the anterior boundary cells is not initiated at the keyhole stage. The lack of cell movement of the ectodermal proventricular cells is consistent with the finding that hedgehog specifically controls Notch target gene activity in the anterior boundary cells. Genetic experiments further identify wingless as a target gene of hedgehog in the anterior boundary cells. wingless, in turn, controls the transcription of the innexin2 gene, which is expressed in the invaginating proventricular cells. When wingless is re-supplied in the genetic background of hedgehog mutants, innexin2 expression is rescued, providing further evidence that innexin2 is a target gene of wingless in the proventriculus primordium. Innexin2 encodes a member of the innexin family of gap junction proteins and is essential for the development of epithelial tissues. In the proventriculus, innexin2 mRNA is initially expressed in the early evagination stage in a broad domain covering both the ectodermal and endodermal precursor cells of the proventriculus primordium. When the ectodermal cells start to invaginate into the proventricular endoderm, innexin2 expression is upregulated in the ectodermal cell layer. Invagination of the ectodermal cells fails in hedgehog, wingless and kropf mutant proventriculi and dye tracer injection experiments demonstrate that hedgehog and kropf mutants show a strong reduction of gap junction communication. These data suggest that the direct coupling of cells via Innexin2-containing gap junctions, which are induced in response to hedgehog and wingless activities, is important for the coordinated movement of the ectodermal cell layer. It is known from extensive studies in mammals that the coupling of cells and tissues via gap junctions enables the diffusion of second messengers, such as Ca2+, inositol-trisphosphate (IP3) or cyclic nucleotides to allow the rapid coordination of cellular behavior during morphogenetic processes such as cell migration and growth control. Cell movement and folding involves a modulation of cell adhesion and of cytoskeletal architecture of the proventricular cells. A functional interaction of innexin2 with the cell adhesion regulator DE-cadherin, which is a core component of adherens junctions has been shown recently by co-immunoprecipitation, yeast two-hybrid studies, and genetic analysis. In mutants of DE-cadherin, Innexin2 is mislocalized and vice versa suggesting that the regulation of cell adhesion and gap junction-mediated communication may be linked. Similar evidence for a coordinated regulation of connexin activity and N-cadherin has been obtained in mammals during migration of neural crest cells (Lechner, 2007).

In kropf mutants or innexin2 knockdown animals, hedgehog, wingless and Delta transcription is strongly reduced as shown by in situ hybridization and by quantitative RT PCR experiments using mRNAs isolated from staged embryos. Furthermore, hedgehog, wingless and Delta are ectopically expressed and their mRNA is upregulated in embryos in which innexin2 is overexpressed. In summary, these experiments provide strong support that the gap junction protein Innexin2 plays an essential role enabling or promoting transcriptional activation of hedgehog, wingless and Delta. These data point towards an essential requirement of gap junction communication for the transcriptional activation of morphogen-encoding genes activating evolutionary conserved signaling cascades essential for patterning in animals. It is of note that gap junctions are established at very early stages of embryonic development, correlating with a maternal and zygotic expression of innexin2 and other innexin family members. kropf mutant animals, which are devoid of maternal and zygotic innexin2 expression are early embryonic lethal and develop no epithelia, consistent with a fundamental role of gap junctions in development, on top of which pattern formation of tissues and organs may occur. It has been shown previously that gap junctions are essential for C. elegans, Drosophila, and vertebrate embryogenesis from early stages onwards (Lechner, 2007 and references therein).

In the nematode C. elegans, a transient network formed by the innexin gap junction protein NSY-5 was recently shown to coordinate left-right asymmetry in the developing nervous system. Previous findings in chick and Xenopus laevis embryos have suggested an essential role of connexin43-mediated gap junction for the determination of the left-right asymmetry of the embryos. Treatment of cultured chick embryos with lindane, which results in a decreased gap junctional communication, frequently unbiased normal left-right asymmetry of Sonic hedgehog and Nodal gene expression, causing the normally left-sided program to be recapitulated. An important role of connexin43 (Cx43)-dependent gap junction communication for sonic hedgehog expression was also observed in limb patterning of the chick wing. Additionally, modulation of gap junctions in Xenopus embryos by pharmacological agents specifically induced heterotaxia involving mirror-image reversals of the heart, gut, and gall bladder. These data in combination with the current findings indicate that the transcriptional regulation of hedgehog and other morphogen-encoding genes by gap junction proteins may be evolutionary conserved between deuterostomes (vertebrates) and protostomes (Drosophila), although the Drosophila innexin gap junction genes share very little sequence homology with the connexin genes. The molecular mechanism underlying innexin2-mediated transcriptional regulation of hedgehog, wingless and Delta is not clear. It has been proposed that the nuclear localization of the carboxy-tail of connexin43 may exert effects on gene expression and growth in cardiomyocytes and HeLa cells. This would infer a cleavage of connexin43 to release the C-terminus, however, in vivo evidence for this event is still lacking. Sequence analysis reveals a nuclear receptor recognition motif within the C-terminus of Innexin2. It has been demonstrated that this recognition motif mediates the interaction of coactivators with nuclear receptors. However, there is no immunohistochemical evidence for a nuclear localization of Innexin2 or the Innexin2 C-terminus in Drosophila embryonic cells indicating that a direct involvement of Innexin2 in regulating transcription of target genes may not occur. The direct association of a transcription factor with gap junctions has been recently proposed for the mouse homolog of ZO-1-associated nucleic acid-binding protein (ZONAB). This transcription factor binds to ZO-1, which is associated with oligodendrocyte, astrocyte and retina gap junctions. It is possible that innexin2-dependent transcriptional regulation may involve a similar type of mechanism: a still unknown transcriptional regulator associated with the C-terminus of innexin2-containing gap junctions could be released upon modulation of gap junction composition thereby modulating the transcription of innexin2-dependent target genes (Lechner, 2007).

The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus)

Stomach cancer is the second most frequent cause of cancer-related death worldwide. Thus, it is important to elucidate the properties of gastric stem cells, including their regulation and transformation. To date, such stem cells have not been identified in Drosophila. Using clonal analysis and molecular marker labeling, this study has identified a multipotent stem-cell pool at the foregut/midgut junction in the cardia (proventriculus). Daughter cells migrate upward either to anterior midgut or downward to esophagus and crop. The cardia functions as a gastric valve and the anterior midgut and crop together function as a stomach in Drosophila; therefore, the foregut/midgut stem cells have been named gastric stem cells (GaSC). JAK-STAT signaling regulates GaSC proliferation, Wingless signaling regulates GaSC self-renewal, and hedgehog signaling regulates GaSC differentiation. The differentiation pattern and genetic control of the Drosophila GaSCs suggest the possible similarity to mouse gastric stem cells. The identification of the multipotent stem cell pool in the gastric gland in Drosophila will facilitate studies of gastric stem cell regulation and transformation in mammals (Singh, 2011).

This study has identified multipotent gastric stem cells at the junction of the adult Drosophila foregut and midgut. The GaSCs express the Stat92E-GFP reporter, wg-Gal4 UAS-GFP, and Ptc, and are slowly proliferating. The GaSCs first give rise to the fast proliferative progenitors in both foregut and anterior midgut. The foregut progenitors migrate downward and differentiate into crop cells. The anterior midgut progenitors migrate upward and differentiate into midgut cells. However, at this stage because of limited markers availability and complex tissues systems at cardia location, it is uncertain how many types of cells are produced and how many progenitor cells are in the cardia. Clonal and molecular markers analysis suggest that cardia cells are populated from gastric stem cells at the foregut/midgut (F/M) junction; however, it cannot be ruled out that there may be other progenitor cells with locally or limited differential potential that may also take part in cell replacement of cardia cells. Nevertheless, the observed differentiation pattern of GaSCs in Drosophila may be similar to that of the mouse gastric stem cells. Gastric stem cells in the mouse are located at the neck-isthmus region of the tubular unit. They produce several terminally differentiated cells with bidirectional migration, in which upward migration towards lumen become pit cells and downward migration results in fundic gland cells (Singh, 2011).

Three signal transduction pathways differentially regulate the GaSC self-renewal or differentiation. The loss of JAK-STAT signaling resulted in quiescent GaSCs; that is, the stem cells remained but did not incorporate BrdU or rarely incorporated BrdU. In contrast, the amplification of JAK-STAT signaling resulted in GaSC expansion (Singh, 2011).

These observations indicate that JAK-STAT signaling regulates GaSC proliferation. In contrast, the loss of Wg signaling resulted in GaSC loss, while the amplification of Wg resulted in GaSC expansion, indicating that Wg signaling regulates GaSC self-renewal and maintenance. Finally, the loss of Hh signaling resulted in GaSC expansion at the expense of differentiated cells, indicating that Hh signaling regulates GaSC differentiation. The JAK-STAT signaling has not been directly connected to gastric stem cell regulation in mammal. However, the quiescent gastric stem cells/progenitors are activated by interferon γ (an activator of the JAK-STAT signal transduction pathway), indicating that JAK-STAT pathways may also regulate gastric stem cell activity in mammals. Amplification of JAK-STAT signaling resulted in expansion of stem cells in germline, posterior midgut and malpighian tubules of adult Drosophila. In the mammalian system, it has been reported that activated STAT contributes to gastric hyperplasia and that STAT signaling regulates gastric cancer development and progression. Wnt signaling has an important function in the maintenance of intestinal stem cells and progenitor cells in mice and hindgut stem cells in Drosophila, and its activation results in gastrointestinal tumor development. Tcf plays a critical role in the maintenance of the epithelial stem cell. Mice lacking Tcf resulted in depletion of epithelial stem-cell compartments in the small intestine as well as being unable to maintain long-term homeostasis of skin epithelia. A recent study even demonstrates that the Wnt target gene Lgr5 is a stem cell marker in the pyloric region and at the esophagus border of the mouse stomach. Further, it has been found that overactivation of the Wnt signaling can transform the adult Lgr5+ve stem cells in the distal stomach, indicating that Wnt signaling may also regulate gastric stem cell self-renewal and maintenance in the mammal. Sonic Hedgehog (Shh) and its target genes are expressed in the human and rodent stomach. Blocking Shh signaling with cyclopamine in mice results in an increase in the cell proliferation of gastric gland, suggesting that Shh may also regulate the gastric stem cell differentiation in mice. These data together suggest that the genetic control of the Drosophila GaSC may be similar to that of the mammalian gastric stem cells (Singh, 2011).

The potential GaSCs niche. In most stem cell systems that have been well characterized to date, the stem cells reside in a specialized microenvironment, called a niche.66 A niche is a subset of neighboring stromal cells and has a fixed anatomical location. The niche stromal cells often secrete growth factors to regulate stem cell behavior, and the stem cell niche plays an essential role in maintaining the stem cells, which lose their stem-cell status once they are detached from the niche (Singh, 2011).

Loss of the JAK-STAT signaling results in the GaSCs being quiescent; the stem cells remain but do not proliferate or rarely proliferate. The Dome receptor is expressed in GaSCs, while the ligand Upd is expressed in adjacent cells. Upd-positive hub cells function as a germline stem cell niche in the Drosophila testis. Further, thia study demonstrated that overexpression of upd results in GaSC expansion, suggesting that the Upd-positive cells may function as a GaSC niche. Furthermore, while Stat92E-GFP expression is regulated by the JAK-STAT signaling in other systems, its expression at the F/M junction seems independent of the JAK-STAT signaling because Stat92E-GFP expression is not significantly disrupted in the Stat92Ets mutant flies, suggesting that the GaSCs may have unique properties (Singh, 2011).

The stomach epithelium undergoes continuous renewal by gastric stem cells throughout adulthood. Disruption of the renewal process may be a major cause of gastric cancer, the second leading cause of cancer-related death worldwide, yet the gastric stem cells and their regulations have not been fully characterized. A more detailed characterization of markers and understanding of the molecular mechanisms control gastric stem cell behavior will have a major impact on future strategies for gastric cancer prevention and therapy. The information gained from this report may facilitate studies of gastric stem cell regulation and transformation in mammals (Singh, 2011).

The putative Na(+)/Cl(-)-dependent neurotransmitter/osmolyte transporter Inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis

Most organisms are able to maintain systemic water homeostasis over a wide range of external or dietary osmolarities. The excretory system, composed of the kidneys in mammals and the Malpighian tubules and hindgut in insects, can increase water conservation and absorption to maintain systemic water homeostasis, which enables organisms to tolerate external hypertonicity or desiccation. However, the mechanisms underlying the maintenance of systemic water homeostasis by the excretory system have not been fully characterized. The present study found that the putative Na(+)/Cl(-)-dependent neurotransmitter/osmolyte transporter inebriated (ine) is expressed in the basolateral membrane of anterior hindgut epithelial cells. This was confirmed by comparison with a known basolateral localized protein, the alpha subunit of Na(+)-K(+) ATPase (ATPalpha). Under external hypertonicity, loss of ine in the hindgut epithelium results in severe dehydration without damage to the hindgut epithelial cells, implicating a physiological failure of water conservation/absorption. It was also found that hindgut expression of ine is required for water conservation under desiccating conditions. Importantly, specific expression of ine in the hindgut epithelium can completely restore disrupted systemic water homeostasis in ine mutants under both conditions. Therefore, ine in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis (Luan 2015).

Water homeostasis is essential for the survival of all organisms. The mammalian kidney and the Malpighian tubule and hindgut of insects play indispensable roles in maintaining water homeostasis over a wide range of external or dietary osmolarities. These organs can increase water conservation and absorption to maintain systemic water homeostasis, which enables organisms to tolerate external hypertonicity or desiccation (Luan 2015).

The mammalian kidney regulates water balance mainly through the antidiuretic hormone (ADH), which enhances water absorption. Failure of antidiuretic mechanisms can result in disrupted systemic water homeostasis, causing pathological conditions like Diabetes Insipidus. Although antidiuretic factors for the enhancement of water absorption, such as Schgr-ITP and CAPA-related peptides, are also present in insects, the mechanisms of water conservation and absorption in the excretory system are not fully characterized, especially in Drosophila (Luan 2015).

Previous studies have shown that loss of the putative Na+/Cl--dependent neurotransmitter/osmolyte transporter ine causes hypersensitivity to dietary hypertonicity in Drosophila; however, the mechanism underlying this effect remains unknown. Ine is a member of the Na+/Cl--dependent neurotransmitter/osmolyte transporter family, which is conserved across invertebrates and vertebrates. Members of this family share several common structural features, including 12 transmembrane domains flanked by intracellular N and C termini, and an extracellular loop between the third and fourth transmembrane domains. These proteins play critical roles in neurotransmission, as well as cellular and systemic homeostasis, by transporting neurotransmitters, osmolytes, and energy metabolites across the plasma membrane. There is sequence similarity between ine and the betaine/GABA transporter (BGT1), a mammalian member of the Na+/Cl--dependent neurotransmitter/osmolyte transporter family. Both BGT1 and ine are expressed in the central nervous system (CNS), as well as organs that perform water absorption, and both are involved in the control of neuronal excitability and tolerance to hypertonicity. This suggests that these two proteins may function through a similar mechanism (Luan 2015).

Betaine, an active organic compound, is the substrate of BGT1 in renal medullary cells; however, the substrate of ine has yet to be identified. Betaine, like other intracellular organic osmolytes, can protect cells from external hypertonicity by balancing high extracellular osmolarity and preserving cell volume without interfering with cell function. However, no direct genetic evidence supports the osmoprotective function of the BGT1-mediated accumulation of betaine in renal medullary cells. Specifically, BGT1 knockout mice are healthy, and renal medullary cells appear to be normal in the hypertonic environment of the renal medulla. Therefore, the physiological function of the Na+/Cl--dependent neurotransmitter/osmolyte transporter in the excretory system remains to be elucidated (Luan 2015).

By investigating the function of ine in Drosophila, an excellent genetic model in which gene expression can be evaluated and manipulated in vivo, the physiological function will be better understood of Na+/Cl--dependent neurotransmitter/osmolyte transporters, including BGT1, in the excretory system. This study elucidates the role of ine in the Drosophila hindgut, and reveal a novel mechanism mediated by ine for the maintenance of systemic water homeostasis (Luan 2015).

This study has demonstrated that the mediation of water conservation/absorption by ine in the hindgut is essential for the maintenance of systemic water homeostasis in Drosophila. In insects, systemic water homeostasis is tightly regulated by the excretory system, including the Malpighian tubules and the hindgut, to ensure a constant internal environment. The dynamic balance between Malpighian tubule secretion and hindgut reabsorption, both of which are controlled by diuretic and antidiuretic hormones or factors, maintains water homeostasis in response to fluctuations in external osmotic conditions. However, in adult Drosophila, the water conservation/absorption mechanisms of the hindgut have not been elucidated. The current results demonstrate that ine is expressed in the basolateral membrane of the hindgut epithelium, suggesting that ine transports substrate from the hemolymph into hindgut epithelial cells. Surprisingly, under conditions of external hypertonicity, the systemic water homeostasis of ine mutant flies is disrupted, whereas that of WT flies is not disturbed. These results demonstrate that hindgut expression of ine mediates water conservation/absorption under external hypertonicity and maintains systemic water homeostasis. These results also suggest possible mechanism for ine function: transport of an osmolyte by ine into the hindgut epithelium increases intracellular molarity, which enhances water conservation/absorption from the hindgut lumen. Such a function would be particularly important in the condition of external hypertonicity, when increased molality in the hindgut lumen prevents osmotic flow of water into hindgut epithelium (Luan 2015).

It could be argued that ine functions through an osmoprotective mechanism, in which increased intracellular accumulation of osmolytes mediated by ine protects the hindgut epithelium from cellular death due to extracellular hypertonicity. However, this study demonstrates that anterior hindgut epithelial cells are not damaged by external hypertonicity in the absence of ine, suggesting that ine function in water conservation/absorption is not secondary to an osmoprotective effect. The existence of other osmolytes or transporters is proposed that function as osmoprotectors, and protect anterior hindgut epithelial cells against lethality under external hypertonicity. The expression of several genes, including some organic transporters, is up-regulated in the hindgut in response to external hypertonicity, supporting this possibility (Luan 2015).

Ine protein is expressed solely in the anterior hindgut. The anterior hindgut is an important site of water absorption, as demonstrated in insects other than Drosophila. In locusts, isosmotic fluid absorption in the anterior hindgut is driven by an apical membrane electrogenic Cl- pump. The antidiuretic hormone Schgr-ITP acts on the locust hindgut via cyclic AMP and GMP to increase the conductance of both K+ and Na+ and to stimulate the Cl- pump. As a result of the increased ion uptake, water absorption increases. It remains unknown, however, whether similar ion-uptake-coupled water absorption mechanisms are present in the Drosophila hindgut. This study found that loss of ine in the anterior hindgut epithelium causes severe dehydration in response to a hypertonic diet, and higher rates of body water loss under desiccation, which suggests the existence of a new mechanism of water conservation/absorption in the hindgut of Drosophila mediated by ine. It was proposed that ine transports osmolytes across the plasma membrane from the hemolymph and accumulates osmolytes within the hindgut epithelium, generating an osmotic driving force to conserve/absorb water from hindgut lumen against external hypertonicity. However, this theory lacks an explanation for how water is transferred into the hemolymph from epithelial cells, and to date, the transporter activity of ine has not been confirmed. The possibility thatine may improve water conservation/absorption through a different, unknown mechanism cannot be ruled out (Luan, 2015)

In addition to the anterior hindgut, the Malpighian tubules, rectum, and midgut also contribute to water absorption and conservation in insects under conditions of external hypertonicity or desiccation. During dehydration stress, the modulation of tyramine signaling in Drosophila Malpighian tubules enhances conservation of body water. Several anti-diuretic factors acting on the Malpighian tubules have been found. For example, CAPA-1 acts on Ncc69, the Na+-K+-2Cl- cotransporter, to increase water absorption through an ion uptake coupled mechanism. In addition, PKG, a cGMP-dependent kinase antagonizes the diuretic effects of tyramine and leukokinin. The rectum can also transport water from lumen to the hemolymph. In the locust, the chloride transport stimulating hormone (CTSH) acts to increase ion-dependent active transport of fluid from the rectum lumen. Finally, the antidiuretic hormone RhoprCAPA-2 inhibits fluid transport into the midgut lumen in Rhodnius prolixus to conserve water. Therefore, ine-mediated water conservation/absorption may not be the only mechanism by which systemic water homeostasis is maintained under external hypertonicity in Drosophila (Luan 2015).

Water is essential for the proper function of virtually all living cells. Organisms have developed mechanisms in the excretory system to maintain water hemostasis for a constant internal milieu under different external osmotic conditions, such as hypertonicity. This study reveals that hindgut expression of ine, a putative Na+/Cl-dependent neurotransmitter/osmolyte transporter, is indispensable for the maintenance of systemic water homeostasis in Drosophila. However, further investigation of the novel mechanism mediated by ine in the hindgut is necessary to fully understand the water conservation and absorption mechanisms of Drosophila hindgut, as well as the physiological functions of the members of the Na+/Cl-dependent neurotransmitter/osmolyte transporter family (Luan 2015)

genes active in gut


Lechner, H., Josten, F., Fuss, B., Bauer, R. and Hoch, M. (2007). Cross regulation of intercellular gap junction communication and paracrine signaling pathways during organogenesis in Drosophila. Dev Biol 310: 23-34. PubMed ID: 17707365

Luan, Z., Quigley, C. and Li, H. S. (2015). The putative Na(+)/Cl(-)-dependent neurotransmitter/osmolyte transporter Inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis. Sci Rep 5: 7993. PubMed. PubMed ID: 25613130

Singh, S. R., Zeng, X., Zheng, Z. and Hou, S. X. (2011). The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus). Cell Cycle 10(7): 1109-20. PubMed ID: 21403464

Skaer, H. (1993). The Alimentary Canal. pp 941-1012. In "The Development of Drosophila melanogaster." Eds. M. Bate and A. Martinez Arias. Cold Spring Harbor Laboratory Press.

date revised: 25 March 2015 

Genes involved in organ development

Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.