Anatomy – Foregut, Midgut, Hindgut - ppt video online download
These are the future foregut and hindgut, respectively. Within the abdominal cavity, the gut is definitively divided into foregut, midgut, and hindgut BASED ON . The primitive gut is divided into the foregut, midgut, and hindgut. . critical for establishing organ domain boundaries between liver and pancreas (Spence et al . The primitive gut can be divided into foregut, midgut, and hindgut, each is the only boundary of the femoral canal that can be cut to release a femoral hernia.
FoxA2 is the master regulator of the anterior primitive gut. FoxA2 mutant mice show defects in cell migration after endodermal specification and thus loss of all foregut and midgut structures; however, hindgut development is unaffected Weinstein et al.Blood Supply to the Gut (Introduction) - Part 1 (Arterial Supply)
Using tetraploid embryo complementation, it was subsequently shown that Foxa2-null cells can form the hindgut but are never incorporated into the developing foregut or midgut Dufort et al. Hhex expression is required for anterior endoderm development and activated by both Nodal and Wnt signaling Martinez-Barbera et al.
The promoter of Hhex has been shown to have both activation and repression domains that are responsive to multiple signaling pathways including Nodal, Wnt, and BMP Rodriguez et al.
Drosophila tissue and organ development: Gut ectoderm - Foregut and hindgut
Sox2 is also required in a dose-dependent manner in the developing foregut Que et al. All of these factors are important throughout the morphogenesis of the anterior part of the gut.
The Caudal-related homeobox transcription factor Cdx2 is required for posterior gut development. Cdx2 expression is highest at E8. Cdx2 is absolutely required in the midgut and hindgut for the formation of the intestine Gao et al. Studies in Caco-2 cells, a colon cancer cell line that is used as a model for the transition of cells from progenitor to differentiation in the intestine, have shown the Cdx2 regulates expression of both progenitor- and differentiation-specific genes Gao et al.
Cdx2 may play a role in mediating chromatin accessibility at these loci Verzi et al. Misexpression of HoxA4 in transgenic mice led to the formation of megacolon Wolgemuth et al. Early studies in the chicken hindgut showed that ectopic expression of Sonic hedgehog in the endoderm was sufficient to induced expression of BMP4 and Hoxd13 in the mesoderm Roberts et al.
In fact, when Hoxd13 was misexpressed in the primitive midgut mesoderm, this was sufficient to cause transformation of the midgut into a structure resembling the hindgut Roberts et al. Loss-of-function mouse models of various Hox genes have also established their importance in intestinal maturation. For instance, ablation of the Hoxa5 gene leads to abnormal stomach development Aubin et al. Importantly, the formation of the ileoceacal valve and the anal sphincter is dependent on the Hoxd cluster Zakany and Duboule Wnt signaling, well known for its role in establishing the anterior—posterior axis of the embryo Huelsken et al.
Similarly, bone morphogenetic protein BMP signaling is required for hindgut development, and the naturally occurring BMP antagonists noggin and chordin are required to allow foregut development Sasai et al. In addition, BMP signaling has been shown to be important in determining cell fates in the foregut during organogenesis, which is discussed in more detail below.
Fibroblast growth factor FGF seems to be expressed in a gradient, with highest expression in the posterior gut Fig. However, varying concentrations of FGF are also required for different lineages that arise from the ventral foregut, such as the liver Jung et al. Retinoic acid signaling has multiple roles in establishing anterior—posterior regional identity. Mice deficient for retinoic acid signaling in the foregut, through deletion of the retinaldehyde dehydrogenase 2 Raldh2 gene or treatment with a pan-retinoic acid receptor RAR antagonist, show failure to develop multiple anterior organs Wendling et al.
Retinoic acid seems to act through regulation of transcription factors with retinoic acid—responsive enhancers including Hoxb1 and Hoxa5 Huang et al. However, there may be multiple additional effects of retinoic acid signaling including activation of other signaling factors such as FGF10 and Sonic hedgehog Shh Ivins et al.
For example, a study of 15 transcription factors expressed within the developing mouse foregut identified more than a dozen unique domains that roughly correspond with particular organs Sherwood et al. Endodermal organ domains were isolated during embryonic development, and gene expression was analyzed by microarray. For instance, the dorsal pancreas domain at embryonic day 9. Using whole-mount immunofluorescence of the dorsal pancreas, subregions were identified with different patterns of coexpression of these factors.
The mechanism behind the complex combinatorial control is organ specific and is discussed in the following sections. Cdx2 is expressed most highly in the hindgut, but its expression extends all the way to the foregut—midgut boundary Silberg et al.
In fact, although the very first duodenal epithelial cell is Cdx2-positive, all cells of the stomach and esophagus lack Cdx2. Cdx2 expression is frequently used as a marker of intestinal metaplasia, a precursor to cancer Bai et al. Specification of the colon and expression of many intestine-specific genes require Cdx2 Gao et al.
Regulation of Hox gene expression along the A—P axis further specifies the intestine and defines areas of major anatomical constrictions Kawazoe et al. A subset of the posterior enteric Hox code is dependent on the presence of Cdx2, indicative of a transcriptional network in the establishment of regional identity in the gut Gao et al. Multiple signaling pathways converge on Cdx2 to regulate intestinal development.
Persistent Wnt signaling in the hindgut regulates the expression of Cdx2. In mice null for the transcriptional effectors of Wnt signaling Tcf1 and Tcf4, the severely posteriorly truncated embryos lack a hindgut altogether, similar to what is seen in Cdx2-null mice Gregorieff et al. 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.
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, 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. 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, 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. 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, 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. 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 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 The mammalian kidney regulates water balance mainly through the antidiuretic hormone ADHwhich 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 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.
Both BGT1 and ine are expressed in the central nervous system CNSas 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 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.
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 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.
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 also suggest possible mechanism for ine function: 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 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.
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 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. 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.
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. 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. 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. 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.
Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons.
The mapping results were validated by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons.
These results provide roadmaps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors Chen, In Drosophila, taste neurons located in sensilla in several body regions sense and distinguish nutritive substances such as sugars, amino acids, and low salt, and potentially harmful ones such as high salt, acids, and a diverse variety of bitter compounds.
Hair-like sensilla on the labellum, distal segments of the legs tarsianterior wing margins, and ovipositor have access to chemicals in external substrates.
Pit-like sensilla taste pegs on the oral surface have access only once the fly extends its proboscis and opens the labellar palps; similar sensilla in the pharynx have access only when food intake is initiated. Based on its anatomical position, the pharynx is considered to act as a gatekeeper to control ingestion, promoting the intake of appetitive foods and blocking that of toxins Chen, Three distinct internal taste organs are present in the adult fly pharynx: The organization and neuronal composition of all three organs, based on both light and electron microscopy data, have been described in detail.
Nine separate sensilla are present in the LSO, of which are innervated by a single mechanosensory neuron each. The remaining three, namedare uniporous sensilla, a feature that ascribes chemosensory function to them. Sensillum 7 is the largest one, with eight chemosensory neurons.
- Transcriptional Networks in Liver and Intestinal Development
Sensilla 8 and 9 have two neurons each one mechanosensory and one chemosensory. Although one study reported two sensilla in the VCSO, this and other studies have observed three sensilla in the VCSO, innervated by a total of eight chemosensory neurons.
The DCSO has two sensilla, each containing three chemosensory neurons. Notwithstanding the availability of detailed anatomical descriptions of pharyngeal taste organs, little is known about their function. The internal location of these organs poses challenges for electrophysiological analysis of taste neurons located within them. Additionally, few molecular tools are currently described to manipulate the function of selected pharyngeal taste neurons Chen, The expression and function of members of several chemosensory receptor gene families such as gustatory receptors Grsionotropic receptors IrsPickpocket Ppk channels, and transient receptor potential channels Trps have been found in external gustatory receptor neurons GRNs of the labellum and the tarsal segments.
A number of Gr- and Ir-GAL4 drivers are also shown to label pharyngeal organs, but only a few, including Gr43a and members of sweet Gr clade, Gr2a, Ir60b, and TrpA1, have been mapped to specific taste neurons Chen, This study generated receptor-to-neuron maps for three pharyngeal taste organs by a systematic expression analysis of chemoreceptor reporter lines that represent Gr, Ir, and Ppk receptor families.
The maps reveal a large and diverse chemoreceptor repertoire in the pharynx. Some receptors are expressed in combinations that are predictive of neuronal sweet or bitter taste function based on analysis of external GRNs. By contrast, some pharyngeal taste neurons express receptor combinations that are distinct from any that have been reported in other organs, leaving open questions about their functional roles.
This study validated he receptor-to-neuron maps derived from reporter gene expression by assessing roles of pharyngeal GRNs predicted to detect L-canavanine, a bitter tastant for which a complete receptor repertoire has been reported. Interestingly, a systematic activation analysis of different classes of pharyngeal taste neurons reveals functional differences between external and internal taste neurons for bitter avoidance and functional subdivision within pharyngeal sweet neurons for sweet acceptance.
Together, this study provides a molecular map of pharyngeal taste organs, which will serve as a resource for future studies of the roles of pharyngeal taste neurons in food evaluation Chen, Internal pharyngeal taste organs are the least explored taste organs, despite their obvious importance in insect feeding behaviors, which are crucial drivers for damaging crops and vectoring disease.
The receptor-to-neuron maps of pharyngeal taste organs suggest a high degree of molecular complexity, with co-expression of different chemoreceptor family members in many pharyngeal GRNs.
In particular, none of the pharyngeal GRNs were found to express Gr genes alone; rather, one or more Ir genes were always expressed in the same neurons.
Gr and Ir genes are also co-expressed in some external sweet and bitter-sensing GRNs. In the pharynx, this study also found co-expression of ppk28 with Ir genes, which has not been described for external GRNs. These observations invite explorations of possible crosstalk, and its functional significance, between the two classes of receptors Chen, Pharyngeal GRNs also exhibit distinctive functional groupings. By contrast, canonical sweet and bitter GRNs appear to segregate in different sensilla in the LSO, which is most well characterized for this perspective.
Moreover, external hairs typically have two to four GRNs, each of which has a distinct functional profile. In the LSO duplications are found L and L are identical, as are L and Lalthough differences between these pairs of GRNs may emerge as additional chemoreceptors are mapped in the pharynx.
Finally, it is difficult to ascribe putative functions to most pharyngeal GRNs based on existing knowledge of receptor function in external counterparts. The L Gr-expressing neuron, for example, does not express members of the sweet clade, but neither does it express any of the common bitter Grs Gr32a, Gr66a, and Gr89a that would corroborate its role as a bitter GRN.
Similarly, with the exception of salt neurons that may express Ir76b alone, there are few known functions for GRNs that solely express Ir genes.
Anatomy – Foregut, Midgut, Hindgut
One possibility is that some of these GRNs possess novel chemoreceptor family ligand interactions. For example, L is involved in sensing sucrose but limiting sugar ingestion, representing an Ir neuron that operates in a negative circuit module for sugar intake. Alternatively, some pharyngeal GRNs may evaluate characteristics other than palatability, such as temperature or viscosity. Ir25a, which is broadly expressed in all 24 pharyngeal GRNs, is required for cool sensing and thermosensing.
It will be worth investigating whether one or more pharyngeal GRNs act to integrate information about temperature and chemical quality of food substrates Chen, Expression analyses also hint at some functional subdivisions between pharyngeal taste organs.
Thus, broader bitter taste function might be expected in the VCSO. Thus, there may be synergistic or hierarchical interactions between LSO and VCSO sweet taste circuits, with the latter coming into play only once the former is activated.
Based on its molecular signature, the V5 neuron was identified as an L-canavanine-sensing neuron in the pharynx. As predicted, feeding avoidance of L-canavanine is dependent on V5. It was thus unexpected that capsaicin-mediated activation of bitter pharyngeal GRNs, which include V5, did not induce strong feeding avoidance either in the absence or presence of sugar. Because the strength and pattern of pharyngeal neuronal activation by bitter tastants or capsaicin is unknown, it is possible that capsaicin response may be weaker than that of canonical bitter tastants.
Alternatively, sweet and bitter inputs from internal and external neurons may be summed differently. It is known that activation of one or few external sweet neurons can lead to proboscis extension, for example, but a larger number of bitter neurons may need to be activated for avoidance Chen, Projections of sugar-sensing GRNs were found in separate ipsilateral regions, whereas those of neurons predicted to detect aversive tastants were found at the midline, suggesting the presence of contralateral termini.
These observations may inform future functional studies of pharyngeal GRNs. L neurons, for example, would be predicted to sense aversive compounds based on the presence of their termini at the midline.
Analysis of pharyngeal GRN projections also suggests distinct connectivity to higher order neuronal circuits. With the molecular tools described here, future investigations of pharyngeal GRNs and pharyngeal taste circuits will provide insight into how internal taste is integrated with external taste to control various aspects of feeding behavior Chen, This study shows that the regulated expression of Tenectin Tnc is critical to shape the Drosophila melanogaster hindgut tube.
Tnc is a secreted protein that fills the embryonic hindgut lumen during tube diameter expansion. Inside the lumen, Tnc contributes to detectable O-Glycans and forms a dense striated matrix. Loss of tnc causes a narrow hindgut tube, while Tnc over-expression drives tube dilation in a dose-dependent manner. Cellular analyses show that luminal accumulation of Tnc causes an increase in inner and outer tube diameter, and cell flattening within the tube wall, similar to the effects of a hydrostatic pressure in other systems.
When Tnc expression is induced only in cells at one side of the tube wall, Tnc fills the lumen and equally affects all cells at the lumen perimeter, arguing that Tnc acts non-cell-autonomously. Moreover, when Tnc expression is directed to a segment of a tube, its luminal accumulation is restricted to this segment and affects the surrounding cells to promote a corresponding local diameter expansion. These findings suggest that deposition of Tnc into the lumen might contribute to expansion of the lumen volume, and thereby to stretching of the tube wall.
Consistent with such an idea, ectopic expression of Tnc in different developing epithelial tubes is sufficient to cause dilation, while epidermal Tnc expression has no effect on morphology. Together, the results show that epithelial tube diameter can be modelled by regulating the levels and pattern of expression of a single luminal glycoprotein Syed, This study shows that the luminal glycoprotein Tnc promotes diameter expansion of the Drosophila hindgut in a dose-dependent manner.
The domain organization of Tnc, its contribution to detectable O-glycans in the hindgut lumen and its ability to form a dense luminal matrix suggest that Tnc has mucin-like characteristics. A possible involvement of mucin-like molecules in tubulogenesis has previously been recognized.
The Caenorhabditis elegans let is a secreted protein with a PTS domain of around amino acids, depending on the splice variant. In mutants for let, the single-celled excretory canals develop massively enlarged lumen by an as yet unknown mechanism. During cyst formation in Madin-Darby Canine Kidney MDCKit has been suggested that the initial separation of apical membranes involves de-adhesive properties conferred by large apically localized glycoproteins.
Recently, it was indeed shown that Podocalyxin is required to separate apical membranes during initial lumen formation in developing blood vessels. Podocalyxin is membrane-bound, and its negatively charged sialic acids are thought to cause electrostatic repulsion of the apical surfaces. Tnc does however appear to function differently from these mucin-like molecules, since it is not required for lumen formation per se, but drives the subsequent step of tube diameter expansion Syed, The function of Tnc also differs from that of the chitinous matrix in the tracheal lumen, as the latter is not needed to increase the luminal volume during diameter expansion, but to shape a uniform diameter.