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PubMed2004

Snail family members and cell survival in physiological and pathological cleft palates.

Palate fusion is a complex process that involves the coordination of a series of cellular changes including cell death and epithelial to mesenchymal transition (EMT). Since members of the Snail family of zinc-finger regulators are involved in both triggering of the EMT and cell survival, we decided to study their putative role in palatal fusion. Furthermore, Snail genes are induced by transforming growth factor beta gene (TGF-beta) superfamily members, and TGF-beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype. Here we show that in the wild-type mouse at the time of fusion, Snail is expressed in a few cells of the midline epithelial seam (MES), compatible with a role in triggering of the EMT in a small subpopulation of the MES. We also find an intriguing relationship between the expression of Snail family members and cell survival associated to the cleft palate condition. Indeed, Snail is expressed in the medial edge epithelial (MEE) cells in TGF-beta(3)-/-mouse embryo palates, where it is activated by the aberrant expression of its inducer, TGF-beta(1), in the underlying mesenchyme. In contrast to Snail-deficient wild-type pre-adhesion MEE cells, Snail-expressing TGF-beta(3) mutant MEE cells survive as they do their counterparts in the chick embryo. Interestingly, Slug is the Snail family member expressed in the chick MEE, providing another example of interchange of Snail and Slug expression between avian and mammalian embryos. We propose that in the absence of TGF-beta(3), TGF-beta(1) is upregulated in the mesenchyme, and that in both physiological (avian) and pathological (TGF-beta(3)-/-mammalian) cleft palates, it induces the expression of Snail genes promoting the survival of the MEE cells and permitting their subsequent differentiation into keratinized stratified epithelium.

Animals↗

PubMed2003

Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.

The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.

Animals↗

PubMed1987

An evaluation of the interactions between freshwater pulmonate snail hosts of human schistosomes and macrophytes.

An account is given of a laboratory investigation designed to evaluate the extent to which the freshwater pulmonate snail Biomphalaria glabrata (Say) can utilize various species of aquatic plants, mainly macrophytes, when presented in the following forms over different time scales: normal plants; dried plant material; homogenized plant material in calcium alginate matrices; water-soluble filtrates of plant homogenates in the medium. The following propositions, derived from the theory of phased coevolution of components of the module consisting of the epiphytic bacteria, algae, snails and macrophytes, are evaluated on the basis of the present results and others including those obtained in this laboratory. That as the snails had become specialized to exploit surface communities of epiphytic algae, decaying plant material and dissolved organic matter (DOM) early in their evolutionary history they would continue to exploit these resources when they later become associated with aquatic macrophytes. That pulmonate snails would tend to be feeding generalists capable of adapting to food of varying chemical composition, given sufficient time, provided it was sufficiently small or flaccid. That although macrophytes and snails show a strong positive relationship, the living macrophyte tissue would be little used by the snails. That the hard outer envelope, inherited from their terrestrial ancestors, would remain as the major defence mechanism of aquatic macrophytes against attack by snails and other aquatic invertebrates. That aquatic macrophytes would invest little in the nutrient deficiency strategy to reduce attack by invertebrates such as snails. That truly aquatic submerged macrophytes would not possess secondary plant compounds (SPC) that would be molluscicidal. Emergent parts of subaquatic or aquatic plants might be expected to be better sources of SPC with molluscicidal factors than submerged aquatic plants. Species of epiphytic or planktonic algae might be better sources of SPC with molluscicidal effects than aquatic macrophytes. That the strategies developed by pulmonate snails for obtaining their energy supplies would not be conducive to rapid speciation. The analysis of the present and other related results supports these propositions. Predictions based on the theory of mutualism involving the snails, macrophytes and other components of the module also receive some support from an analysis of the present results. The additional empirical work that could be undertaken to test this theory is briefly discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2004

Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.

The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here we show that mammalian Snail requires histone deacetylase (HDAC) activity to repress E-cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Snail. Moreover, overexpression of Snail is correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter, and TSA treatment in Snail-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate that Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression. Our results establish a direct causal relationship between Snail-dependent repression of E-cadherin and the modification of chromatin at its promoter.

Animals↗

PubMed2004

The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation.

Snail, a transcriptional repressor of E-cadherin expression, is involved in epithelial-mesenchymal transitions during development. We demonstrate that Snail activity is not restricted to E-cadherin downregulation. Expression of tight junction proteins, including claudin-1, occludin and ZO-1, was downregulated in MDCK cells exogenously expressing Snail protein. Although occludin mRNA levels were downregulated by Snail expression, the transcription of claudin-1 and ZO-1 were unaffected. Reporter assays using the claudin-1 promoter region revealed that promoter activity was not affected by Snail overexpression. Decreased synthesis of claudin-1 protein was observed, however, suggesting that Snail may act in translation initiation. Snail expression also altered the splicing pattern of p120. The levels of mRNA encoding the epithelial variant decreased, while the fibroblastic mRNA form increased. Although ectopic E-cadherin expression resulted in a downregulation of Snail-induced fibronectin expression, fibroblastic morphology was affected only minimally; the expression of tight junctional proteins remained at low levels. These results indicate that Snail is involved in both the direct transcriptional repression of genes, such as E-cadherin and occludin, and post-transcriptional events, including downregulation of claudin-1. These data support the idea that Snail is a transcription factor possessing pleiotropic activities.

Alternative Splicing↗

PubMed2003

Effects of snail size and age on the prevalence and intensity of avian schistosome infection: relating laboratory to field studies.

Both the prevalence and intensity of patent infection by avian schistosomes (Trichobilharzia ocellata) increase with increasing size of lymnaeid snails (Stagnicola elrodi) collected in Flathead Lake, Montana. Because the size and age of a snail are positively correlated, snails of different sizes may have experienced differential duration of exposure to and development of infection. Another possibility is that infection itself induces snail gigantism. Each of these possibilities could lead to increased prevalence and intensity of infection among the oldest-largest snails. To decouple size variation from many correlated effects of age and to test for parasite-induced gigantism, laboratory experiments standardized snail size-age-at-infection, exposure history, inoculating dose, and duration of infection. The positive relationship between size and prevalence was eliminated in the laboratory, but the relationship between size and infection intensity remained. Laboratory results thus suggest that infection intensity is related to snail size per se, whereas prevalence in the field is related to snail size only through the correlation between size and age. In addition, under these experimental conditions, infected snails were no larger than uninfected snails, so the patterns observed in the field might not be attributable to gigantism.

Animals↗

PubMed1999

[Longitudinal observation on a schistosome-infected snail spot as a source of infection in a mountainous village of Dali city].

AIM: To observe longitudinally the changes in survival and infection rate of Oncomelania snails in a positive snail spot in Yunnan. METHODS: A positive snail spot in a ditch in Shalimuzhuang Village, Dali City, was continually observed on the changes in the density of snail population and natural infection rate of the snails by random environmental sampling for 8 times in 4 successive years. RESULTS: During the 8 times of snail survey, living snails were found relatively stable in the ditch, in which positive snails were obtained in 6 occasions, the average infection rate being 3.99%. CONCLUSION: The density and the positive rate of snails in the mountain region remains relatively stable as a source of human infection. Elimination of the positive snail spots is necessary for controlling schistosomiasis.

Animals↗

PubMed2002

[Sensitivity of Oncomelania snail to niclosamide in China].

OBJECTIVE: To understand the variation in response of Oncomelania hupensis to niclosamide. METHODS: Snails were collected from 37 sampling areas distributed in 10 provinces (municipalities) using random environmental sampling methods in accordance with the different types and categories of snail habitats. In laboratory the snails were immersed in solutions of niclosamide for 24 and 48 hours at 25 degrees C. RESULTS: 1.0 mg/L niclosamide showed 100% killing effect on snails in 24 hours. The LC50 concentrations for snails immersed for 24 hours ranged from 0.0320 to 0.1689 mg/L with a mean value of 0.0920 mg/L. 0.5 mg/L niclosamide showed 100% killing effect on snails in 48 hours. The LC50 values for snails immersed for 48 hours ranged between 0.0299 and 0.1114 mg/L with a mean of 0.0627 mg/L. There is a significant difference in snail sensitivity to niclosamide between sampling areas. CONCLUSION: The sensitivity to niclosamide varied in snails from different sampling fields, but the chemical in a concentration of 1.0 mg/L showed 100% effect of killing snails, which is consistent to the manual of schistosomiasis control.

Animals↗

PubMed2003

Transcriptional repressor snail and progression of human hepatocellular carcinoma.

PURPOSE: Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. EXPERIMENTAL DESIGN AND RESULTS: Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. CONCLUSIONS: The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.

Aged↗

PubMed2005

The contamination of wild watercress with Fasciola hepatica in central France depends on the ability of several lymnaeid snails to migrate upstream towards the beds.

As most natural watercress beds in central France are located upstream of the permanent habitats of two lymnaeid species, Galba truncatula and Omphiscola glabra, field investigations were made from 1999 to 2004 on 67 beds to determine why the contamination of watercress with Fasciola hepatica is irregular over time in these sites, while definitive hosts, especially lagomorphs, are regularly found infected around them. Snails are able to migrate upstream in winter and spring towards the beds, and a 4-year survey demonstrated the existence of annual variation in the colonization of these sites by snails. In the 45 beds irregularly contaminated with F. hepatica over time, 37.7-62.2%, according to the year, were not populated by lymnaeids, in spite of the presence of snail populations downstream. G. truncatula was found alone in 8.8-13.3% of sites and was the first colonizing snail in 24.3-33.3% when the two lymnaeid species successively settled in these waterholes. The colonizing ability of O. glabra was more limited, as it was observed alone in 2.2% of beds and was the first colonizing snail in only 2.2-20% of them. The distances covered by these snails significantly increased with increasing migration time. After migration, a few overwintering snails (3.8% of G. truncatula and 6.8% of O. glabra) are able to colonize the beds, but their numbers decreased when the distance of migration was greater. O. glabra migrated more quickly and reached more watercress beds than G. truncatula. However, this did not influence the natural infections of snails, which were more frequent in the F1 of G. truncatula. The variability observed in the colonization of beds by snails might explain the regular or irregular contamination of wild watercress by metacercariae of F. hepatica. One of the factors which may explain this variability is the occurrence of showers in spring, so that a few snails are able to reach watercress beds after their upstream migration.

Animals↗

PubMed1995

Geographic compatibility of the freshwater snail Bulinus globosus and schistosomes from the Zimbabwe highveld.

Populations of Bulinus globosus were sampled from two rivers, 60 km apart, in northern Zimbabwe, and offspring from each geographic strain reared in the laboratory. Schistosomes were harvested from each strain and also maintained in the laboratory. Cross-infection experiments were conducted, whereby snails of both geographic strains were exposed to parasites of both geographic strains. Compatibility was found to be related to: (i) the geographic origin of the snail, and (ii) an interaction between the geographic origin of snail and parasite, such that sympatric combinations of snails and parasites produced a greater proportion of compatible infections than allopatric combinations. Cercarial output of infected snails was found to be related to the geographic origin of the parasite, but not of that of the snail. It is suggested that, as the snails used were laboratory bred and naive to schistosome infection, differences in snail-schistosome compatibility were genetically determined, rather than an adaptive response. This study supports earlier work which suggests the existence of geographic compatibility amongst natural populations of snails and trematodes, indicative of either increased infectivity by the parasite, or decreased resistance by the snail.

Animals↗

PubMed1996

Biogenic monoamines in the freshwater snail, Biomphalaria glabrata: influence of infection by the human blood fluke, Schistosoma mansoni.

The biogenic monoamines, serotonin (5-HT), dopamine (DA) and L-dopa were measured using high performance liquid chromatography with electrochemical detection (HPLC-ED) in the extracts of the central nervous system (CNS) and plasma of uninfected freshwater snails, Biomphalaria glabrata, and in snails at 7, 14, 21 and 28 days postexposure (PE) to the miracidia of the human blood fluke, Schistosoma mansoni. Relative to age-matched uninfected snails, a general depression of biogenic amine levels was observed in the plasma (cell-free haemolymph) and the CNS of infected snails, especially during the latter phase of the prepatency period. Significant decreases were first observed in the CNS of infected snails beginning at Day 14 PE for DA and 5-HT and Day 21 PE for L-dopa. Parasite-exposed snails also exhibited an early and persistent suppression of plasma 5-HT concentrations, starting at 7 days PE and continuing throughout the infection test period. In order to determine the effect of 5-HT on reproduction and, thereby, establish a possible relationship between the observed parasite-induced reduction in 5-HT levels and parasitic castration, the effect of exogenous 5-HT on individual infected and uninfected B. glabrata was investigated. Repeated treatment with 10 microM 5-HT promoted both ovulation and oviposition in B. glabrata. Snails treated with 5-HT consistently layed more eggs than did sham-treated controls. Infected snails that were treated with 5-HT exhibited similar egg-laying rates as those of both serotonin-treated and untreated, uninfected snail groups, thus reversing the castrating effects of larval infection. These findings suggest that 5-HT acts as a stimulant for egg production in B. glabrata, and that parasitic castration may be due, at least in part, to larval-induced suppression of 5-HT in the snail's CNS and plasma during the course of infection with S. mansoni.

Animals↗

PubMed2004

Free radical scavengers in susceptible/resistant Biomphalaria alexandrina snails before and after infection.

The activities of catalase (Cat), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione transferase (GST), glucose-6-phosphate dehydrogenase (G6PD) and glyceraldehyde3-phosphate dehydrogenase (G3PD) were studied in tissue and hemolymph of susceptible (S) (EgBS(2)) and resistant (R) (EgBR(2)) Biomphalaria alexandrina snails. The results showed that CAT and GST were higher in the hemolymph of snails susceptible to Schistosoma mansoni than in that of snails resistant to infestation, while SOD and G3PD were lower in the susceptible snails. The role of these enzymes as free radical scavengers was traced 1 and 24 h after infection of the two snail lines with S. mansoni. Moreover, the activities of SOD and G3PD were also measured 2 and 4 weeks post infection. The results revealed that the overall enzymatic activities were higher in susceptible than in resistant snail tissues. After 1 h of infection, all enzymes were increased in R and S snails except GST and G6PD which decreased in S snails. After 24 h of infection, GST increased in S snails and G3PD decreased in both S and R snails while other enzymes reached normal levels.

Animals↗

PubMed1998

Chemo-orientation of echinostome cercariae towards their snail hosts: the stimulating structure of amino acids and other attractants.

The cercariae of Pseudechinoparyphium echinatum and Echinostoma revolutum locate their host snails by turning back when swimming in decreasing gradients of the small molecular weight fraction (< 500) of snail conditioned water. Fractionation and chemical modifications of snail conditioned water from Lymnaea stagnalis showed that amino acids are necessary for the stimulating activity of snail conditioned water. A complete mixture of amino acids in concentrations determined from snail conditioned water had a high attraction. However, differently composed mixtures of amino acids and even single amino acids also had the same attraction as this complete mixture when used in concentrations corresponding to the total concentration of amino acids in snail conditioned water. Experiments with analogues and derivatives of amino acids showed that the primary alpha-amino group and the alpha-carboxyl group are necessary for the full effectiveness of amino acids. The highest effect was elicited by L-amino acids with a primary alpha-amino group, whereas the amino acid type and the chain length seemed to be unimportant. However, the full attraction of snail conditioned water was not achieved by amino acids alone. Chemical modifications of snail conditioned water suggested that the additional stimuli were neither inorganic ions nor organic acids or lipids. As the full attraction of snail conditioned water was obtained when the amino acid mixture of snail conditioned water was combined with its content of urea and ammonia, we conclude that the cercariae use only these excretory products as additional signals for their chemo-orientation. Chemo-orientation to amino acids, urea and ammonia seems to reflect a strategy to locate a broad spectrum of aquatic hosts.

Amino Acids↗

PubMed2001

Further characterization of passively transferred resistance to Schistosoma mansoni in the snail intermediate host Biomphalaria glabrata.

A heat-labile plasma factor from genetically resistant 10-R2 Biomphalaria glabrata snails confers passively transferred resistance (PTR) to Schistosoma mansoni when injected into susceptible snails within 24-hr of exposure to miracidia. However, no additional details on PTR have emerged since the initial 1984 report, nor has the plasma resistance factor been characterized. In the present study, new information is provided on the occurrence of resistance factor in plasma of additional types of snails, effect of "priming" resistant plasma donors by prior exposure to miracidia, duration of PTR, molecular weight of resistance factor, and fate of sporocysts in snails with PTR. Susceptible NIH albino snails injected 24 hr prior to exposure to miracidia with individual samples of plasma from a different strain (Salvador B. glabrata) or a different species (B. obstructa) of nonsusceptible snail displayed infection prevalences of 49% or 59% of control levels, respectively, whereas injections of homologous plasma had no effect. PTR was not enhanced by prior exposure of resistant Salvador plasma donors to miracidia. Unexpectedly, PTR induced by injections of Salvador plasma persisted for at least 21 days. The molecular weight of the resistance factor(s) was between 10 and 30 kDa, based on results of centrifugal ultrafiltration. A significantly higher proportion of dead sporocysts occurred in histological sections of tentacles from snails injected with Salvador plasma than in tentacles of snails injected with NIH albino plasma at 7 days postexposure to miracidia. Most dead sporocysts in Salvador plasma-injected snails were undergoing gradual degeneration, rather than rapid, hemocyte-mediated destruction, as occurred in Salvador snails.

Animals↗

PubMed1975

Clonorchis sinensis in Kyungpook Province, Korea: 1. Distribution and demonstration of the cercaria of Clonorchis sinensis from snail, Parafossarulus manchouricus Bourgigant.

Studies were conducted in rivers in Kyungpook Province, Korea from July 1970 to September 1974 to determine the stations where Parafossarulus manchouricus, the intermediate snail host of Clonorchis sinensis, are abundant, and the infection rates of these snails with the cercaria of Clonorchis sinensis. Snail collections were made during four consecutive summers(July to September in each year). Ten snail habitats were found. The population density of the snails per square meter of the river bottom ranged from 25 to 250. The highest population of snails was encountered at the Dong-chon station. Cercaria studies by means of the immersing and crushing technics indicated surprisingly low rate of Clonorchis sinensis infection among the snails examined. The proportion of infected snails in Kyungpook Province was 0.8 per thousand of all snails examined. Results indicated that the Parafossarulus manchouricus exists in limited areas within the rivers under study and the infection of the snail with the cercaria of Clonorchis sinensis is very low.

Journal Article↗

PubMed1996

Male reproductive success of Schistosoma mansoni-infected Biomphalaria glabrata snails.

Infection of Biomphalaria glabrata by Schistosoma mansoni results in a dramatic reduction in the snail's ability to produce eggs. We studied the ability of such parasitically castrated snails to fertilize the eggs of uninfected snails. Pigmented B. glabrata snails (13141 stock) were infected with S. mansoni miracidia and reared individually until they ceased laying eggs. These infected snails were then given the opportunity to mate with uninfected albino (NMRI) snails. Each of the infected snails was paired with a different albino partner each subsequent week. Sperm transfer by the infected snails was evident from the production of pigmented progeny by the uninfected albino snails. Infected snails successfully acted as males for up to 6 wk after parasitic castration had occurred. The duration of allosperm use by uninfected recipients was lengthy, regardless of the infection status of the pigmented sperm donor.

Animals↗

PubMed1961

Biological studies on the snail, Bulinus truncatus, in Central Iraq.

This paper presents some results of field and laboratory studies on Bulinus truncatus, the snail intermediate host of urinary bilharziasis in Iraq, made in 1958 as part of the work of the WHO Bilharziasis Control Project in that country.Observations on the linear distribution and size composition of Bulinus populations in the canals of central Iraq indicate that molluscicides might most suitably be applied in May before the entire snail population reaches breeding size, or early in November when most snails are juveniles. However, laboratory experiments appear to show that isolation of individual bulinid snails does not diminish, but may actually increase, their egg-laying capacity in comparison with that of grouped snails; this suggests that, even if the snail population were drastically reduced by treatment of the canals and all further importation of snails rendered impossible, the snail population would nevertheless soon renew itself from the few individuals remaining.Results are also given of laboratory experiments on egg masses, hatching and growth of B. truncatus and on the egg-laying of random populations of that snail.

Animals↗