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John Klingensmith - One of the best experts on this subject based on the ideXlab platform.
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one shall become two separation of the esophagus and trachea from the common Foregut tube
Developmental Dynamics, 2015Co-Authors: Katherine Kretovich Billmyre, Mary R Hutson, John KlingensmithAbstract:The alimentary and respiratory organ systems arise from a common endodermal origin, the anterior Foregut tube. Formation of the esophagus from the dorsal region and the trachea from the ventral region of the Foregut primordium occurs via a poorly understood compartmentalization process. Disruption of this process can result in severe birth defects, such as esophageal atresia and tracheoesphageal fistula (EA/TEF), in which the lumina of the trachea and esophagus remain connected. Here we summarize the signaling networks known to be necessary for regulating dorso-ventral patterning within the common Foregut tube and cellular behaviors that may occur during normal Foregut compartmentalization. We propose that dorso-ventral patterning serves to establish a lateral region of the Foregut tube that is capable of undergoing specialized cellular rearrangements, culminating in compartmentalization. We review established as well as new rodent models that may be useful in addressing this hypothesis. Finally, we discuss new experimental models that could help elucidate the mechanism behind Foregut compartmentalization. An integrated approach to future Foregut morphogenesis research will allow for a better understanding of this complex process.
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one shall become two separation of the esophagus and trachea from the common Foregut tube
Developmental Dynamics, 2015Co-Authors: Katherine Kretovich Billmyre, Mary R Hutson, John KlingensmithAbstract:The alimentary and respiratory organ systems arise from a common endodermal origin, the anterior Foregut tube. Formation of the esophagus from the dorsal region and the trachea from the ventral region of the Foregut primordium occurs by means of a poorly understood compartmentalization process. Disruption of this process can result in severe birth defects, such as esophageal atresia and tracheo-esphageal fistula (EA/TEF), in which the lumina of the trachea and esophagus remain connected. Here we summarize the signaling networks known to be necessary for regulating dorsoventral patterning within the common Foregut tube and cellular behaviors that may occur during normal Foregut compartmentalization. We propose that dorsoventral patterning serves to establish a lateral region of the Foregut tube that is capable of undergoing specialized cellular rearrangements, culminating in compartmentalization. We review established as well as new rodent models that may be useful in addressing this hypothesis. Finally, we discuss new experimental models that could help elucidate the mechanism behind Foregut compartmentalization. An integrated approach to future Foregut morphogenesis research will allow for a better understanding of this complex process.
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bmp antagonism by noggin is required in presumptive notochord cells for mammalian Foregut morphogenesis
Developmental Biology, 2014Co-Authors: Sarah R Fausett, Lisa J Brunet, John KlingensmithAbstract:Esophageal atresia with tracheoesophageal fistula (EA/TEF) is a serious human birth defect, in which the esophagus ends before reaching the stomach, and is aberrantly connected with the trachea. Several mouse models of EA/TEF have recently demonstrated that proper dorsal/ventral (D/V) patterning of the primitive anterior Foregut endoderm is essential for correct compartmentalization of the trachea and esophagus. Here we elucidate the pathogenic mechanisms underlying the EA/TEF that occurs in mice lacking the BMP antagonist Noggin, which display correct dorsal/ventral patterning. To clarify the mechanism of this malformation, we use spatiotemporal manipulation of Noggin and BMP receptor 1A conditional alleles during Foregut development. Surprisingly, we find that the expression of Noggin in the compartmentalizing endoderm is not required to generate distinct tracheal and esophageal tubes. Instead, we show that Noggin and BMP signaling attenuation are required in the early notochord to correctly resolve notochord cells from the dorsal Foregut endoderm, which in turn, appears to be a prerequisite for Foregut compartmentalization. Collectively, our findings support an emerging model for a mechanism underlying EA/TEF in which impaired notochord resolution from the early endoderm causes the Foregut to be hypo-cellular just prior to the critical period of compartmentalization. Our further characterizations suggest that Noggin may regulate a cell rearrangement process that involves reciprocal E-cadherin and Zeb1 expression in the resolving notochord cells.
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compartmentalization of the Foregut tube developmental origins of the trachea and esophagus
Wiley Interdisciplinary Reviews-Developmental Biology, 2012Co-Authors: Sarah R Fausett, John KlingensmithAbstract:The mammalian trachea and esophagus share a common embryonic origin. They arise by compartmentalization of a single Foregut tube, composed of Foregut endoderm (FGE) and surrounding mesenchyme, around midgestation. Aberrant compartmentalization is thought to lead to relatively common human birth defects, such as esophageal atresia (EA) and tracheoesophageal fistula (EA/TEF), which can prevent or disrupt a newborn infant's ability to feed and breathe. Despite its relevance to human health, morphogenesis of the anterior Foregut is still poorly understood. In this article, we provide a comprehensive review of trachea and esophagus formation from a common precursor, including the embryonic origin of the FGE, current models for Foregut morphogenesis, relevant human birth defects, insights from rodent models, and the emerging picture of the mechanisms underlying normal and abnormal Foregut compartmentalization. Recent research suggests that a number of intercellular signaling pathways and several intracellular effectors are essential for correct formation of the trachea and esophagus. Different types of defects in the formation of either ventral or dorsal Foregut tissues can disrupt compartmentalization in rodent models. This implies that EA/TEF defects in humans may also arise by multiple mechanisms. Although our understanding of Foregut compartmentalization is growing rapidly, it is still incomplete. Future research should focus on synthesizing detailed information gleaned from both human patients and rodent models to further our understanding of this enigmatic process.
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morphogenesis of the trachea and esophagus current players and new roles for noggin and bmps
Differentiation, 2006Co-Authors: Jianwen Que, John Klingensmith, Murim Choi, Joshua W Ziel, Brigid L M HoganAbstract:The development of the anterior Foregut of the mammalian embryo involves changes in the behavior of both the epithelial endoderm and the adjacent mesoderm. Morphogenetic processes that occur include the extrusion of midline notochord cells from the epithelial definitive endoderm, the folding of the endoderm into a Foregut tube, and the subsequent separation of the Foregut tube into trachea and esophagus. Defects in Foregut morphogenesis underlie the constellation of human birth defects known as esophageal atresia (EA) and tracheoesophageal fistula (TEF). Here, we review what is known about the cellular events in Foregut morphogenesis and the gene mutations associated with EA and TEF in mice and humans. We present new evidence that about 70% of mouse embryos homozygous null for Nog, the gene encoding noggin, a bone morphogenetic protein (Bmp) antagonist, have EA/TEF as well as defects in lung branching. This phenotype appears to correlate with abnormal morphogenesis of the notochord and defects in its separation from the definitive endoderm. The abnormalities in Foregut and lung morphogenesis of Nog null mutant can be rescued by reducing the gene dose of Bmp4 by 50%. This suggests that normal Foregut morphogenesis requires that the level of Bmp4 activity is carefully controlled by means of antagonists such as noggin. Several mechanisms are suggested for how Bmps normally function, including by regulating the intercellular adhesion and behavior of notochord and Foregut endoderm cells. Future research must determine how Noggin/Bmp antagonism fits into the network of other factors known to regulate tracheal and esophagus development, both in mouse or humans.
Kevin D. Kohl - One of the best experts on this subject based on the ideXlab platform.
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metagenomic sequencing provides insights into microbial detoxification in the guts of small mammalian herbivores neotoma spp
FEMS Microbiology Ecology, 2018Co-Authors: Kevin D. Kohl, Kelly F. Oakeson, Colin Dale, Aaron W Miller, Teri J Orr, Jennifer S Forbey, Caleb D Phillips, Robert B. WeissAbstract:Microbial detoxification of plant toxins influences the use of plants as food sources by herbivores. Stephen's woodrats (Neotoma stephensi) specialize on juniper, which is defended by oxalate, phenolics and monoterpenes, while closely related N. albigula specialize on cactus, which only contains oxalate. Woodrats maintain two gut chambers harboring dense microbial communities: a Foregut chamber proximal to the major site of toxin absorption, and a cecal chamber in their hindgut. We performed several experiments to investigate the location and nature of microbial detoxification in the woodrat gut. First, we measured toxin concentrations across gut chambers of N. stephensi. Compared to food material, oxalate concentrations were immediately lower in the Foregut, while concentrations of terpenes remained high in the Foregut, and were lowest in the cecal chamber. We conducted metagenomic sequencing of the Foregut chambers of both woodrat species and cecal chambers of N. stephensi to compare microbial functions. We found that most genes associated with detoxification were more abundant in the cecal chambers of N. stephensi. However, some genes associated with degradation of oxalate and phenolic compounds were more abundant in the Foregut chambers. Thus, microbial detoxification may take place in various chambers depending on the class of chemical compound.
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Patterns of host gene expression associated with harboring a Foregut microbial community
BMC Genomics, 2017Co-Authors: Kevin D. Kohl, Kelly F. Oakeson, Diane Dunn, David K. Meyerholz, Colin Dale, Robert B. Weiss, M. Denise DearingAbstract:Background Harboring Foregut microbial communities is considered a key innovation that allows herbivorous mammals to colonize new ecological niches. However, the functions of these chambers have only been well studied at the molecular level in ruminants. Here, we investigate gene expression in the Foregut chamber of herbivorous rodents and ask whether these gene expression patterns are consistent with results in ruminants. We compared gene expression in Foregut tissues of two rodent species: Stephen’s woodrat ( Neotoma stephensi ), which harbors a dense Foregut microbial community, and the lab rat ( Rattus norvegicus ), which lacks such a community. Results We found that woodrats have higher abundances of transcripts associated with smooth muscle processes, specifically a higher expression of the smoothelin-like 1 gene, which may assist in contractile properties of this tissue to retain food material in the Foregut chamber. The expression of genes associated with keratinization and cornification exhibited a complex pattern of differences between the two species, suggesting distinct molecular mechanisms. Lab rats exhibited higher abundances of transcripts associated with immune function, likely to inhibit microbial growth in the Foregut of this species. Conclusions Some of our results were consistent with previous findings in ruminants (high expression of facilitative glucose transporters, lower expression of B4galnt2 ), suggestive of possible convergent evolution, while other results were unclear, and perhaps represent novel host-microbe interactions in rodents. Overall, our results suggest that harboring a Foregut microbiota is associated with changes to the functions and host-microbe interactions of the Foregut tissues.
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herbivorous rodents neotoma spp harbour abundant and active Foregut microbiota
Environmental Microbiology, 2014Co-Authors: Kevin D. Kohl, Aaron W Miller, James E Marvin, Roderick I Mackie, Denise M DearingAbstract:Symbiotic gut microbes have facilitated the success of herbivorous mammals, which are generally grouped into Foregut- and hindgut-fermenters. However, rodents are primarily herbivorous and exhibit a variety of gastrointestinal anatomies. Most rodents house microbes in hindgut chambers, such as the caecum and colon. Some rodents also exhibit stomach segmentation with a Foregut chamber proximal to the stomach. For over a century, scientists have hypothesized that this Foregut chamber houses a microbial community, yet this has never been explicitly examined. We investigated the capacity of each of the gut regions to house microbes by measuring size, pH, bacterial cell density, concentrations of microbial metabolites and digesta transit time in woodrats (Neotoma spp.). We also compared microbial communities across gut chambers, as well as faeces, using 16S rRNA sequencing. This allowed us to test the appropriateness of using faeces as a proxy for microbial communities of other gut chambers. We found that woodrats house Foregut microbial communities with similar density and volatile fatty acid concentrations to rumen ecosystems. Resident microbial communities varied between gut chambers, and faecal bacterial communities were significantly different from caecal and colonic communities. The Foregut microbiota may provide a number of physiological services to the host.
Fei Gao - One of the best experts on this subject based on the ideXlab platform.
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bacterial community composition in the gut content and ambient sediment of sea cucumber apostichopus japonicus revealed by 16s rrna gene pyrosequencing
PLOS ONE, 2014Co-Authors: Fei GaoAbstract:The composition of the bacterial communities in the contents of the Foregut and hindgut of the sea cucumber Apostichopus japonicus and in the ambient surface sediment was surveyed by 16S rRNA gene 454-pyrosequencing. A total of 188,623 optimized reads and 15,527 operational taxonomic units (OTUs) were obtained from the ten gut contents samples and four surface sediment samples. The sequences in the sediments, Foregut contents, and hindgut contents were assigned to 38.0±4.7, 31.2±6.2 and 27.8±6.5 phyla, respectively. The bacterial richness and Shannon diversity index were both higher in the ambient sediments than in the gut contents. Proteobacteria was the predominant phylum in both the gut contents and sediment samples. The predominant classes in the Foregut, hindgut, and ambient sediment were Holophagae and Gammaproteobacteria, Deltaproteobacteria and Gammaproteobacteria, and Gammaproteobacteria and Deltaproteobacteria, respectively. The potential probiotics, including sequences related to Bacillus, lactic acid bacteria (Lactobacillus, Lactococcus, and Streptococcus) and Pseudomonas were detected in the gut of A. japonicus. Principle component analysis and heatmap figure showed that the Foregut, hindgut, and ambient sediment respectively harbored different characteristic bacterial communities. Selective feeding of A. japonicus may be the primary source of the different bacterial communities between the Foregut contents and ambient sediments.
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Bacterial Community Composition in the Gut Content and Ambient Sediment of Sea Cucumber Apostichopus japonicus Revealed by 16S rRNA Gene Pyrosequencing
2014Co-Authors: Fei Gao, Jie Tan, Jingping Yan, Huiling SunAbstract:The composition of the bacterial communities in the contents of the Foregut and hindgut of the sea cucumber Apostichopus japonicus and in the ambient surface sediment was surveyed by 16S rRNA gene 454-pyrosequencing. A total of 188,623 optimized reads and 15,527 operational taxonomic units (OTUs) were obtained from the ten gut contents samples and four surface sediment samples. The sequences in the sediments, Foregut contents, and hindgut contents were assigned to 38.064.7, 31.266.2 and 27.866.5 phyla, respectively. The bacterial richness and Shannon diversity index were both higher in the ambient sediments than in the gut contents. Proteobacteria was the predominant phylum in both the gut contents and sediment samples. The predominant classes in the Foregut, hindgut, and ambient sediment were Holophagae and Gammaproteobacteria, Deltaproteobacteria and Gammaproteobacteria, and Gammaproteobacteria and Deltaproteobacteria, respectively. The potential probiotics, including sequences related to Bacillus, lactic acid bacteria (Lactobacillus, Lactococcus, and Streptococcus) and Pseudomonas were detected in the gut of A. japonicus. Principle component analysis and heatmap figure showed that the Foregut, hindgut, and ambient sediment respectively harbored different characteristic bacterial communities. Selective feeding of A. japonicus may be the primary source of the different bacterial communities betwee
Katherine C Bishop - One of the best experts on this subject based on the ideXlab platform.
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ciliated hepatic Foregut cyst a report of 6 cases and a review of the english literature
Diagnostic Pathology, 2015Co-Authors: Katherine C Bishop, Carmen M Perrino, Marianna B Ruzinova, Elizabeth M BruntAbstract:Background Ciliated hepatic Foregut cyst (CHFC) is a rare cystic lesion most commonly identified in segment 4 of the liver that arises from the embryonic Foregut. The classic histologic pattern is comprised of 4 distinct layers (inner ciliated epithelial lining, smooth muscle, loose connective tissue, fibrous capsule). Although rare, cases of metaplastic and malignant epithelial lining have been described in CHFC.
Michael Locketz - One of the best experts on this subject based on the ideXlab platform.
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ciliated hepatic Foregut cyst a rare cystic liver lesion
Journal of Gastrointestinal Surgery, 2008Co-Authors: John Shaw, J E J Krige, S J Beningfield, Michael LocketzAbstract:Ciliated hepatic Foregut cysts are an unusual congenital cause of cystic liver lesions. Although most are benign, 4.4% of reported cases have been shown to harbor squamous cell carcinoma. Diagnostic uncertainty or misdiagnosis frequently results in surgical exploration. We present a case of a ciliated hepatic Foregut cyst and review this uncommon condition.