The Experts below are selected from a list of 8934 Experts worldwide ranked by ideXlab platform
Vassilis Pachnis - One of the best experts on this subject based on the ideXlab platform.
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emerging roles of gut microbiota and the immune System in the development of the Enteric Nervous System
Journal of Clinical Investigation, 2015Co-Authors: Panagiotis S Kabouridis, Vassilis PachnisAbstract:The Enteric Nervous System (ENS) consists of neurons and glial cells that differentiate from neural crest progenitors. During embryogenesis, development of the ENS is controlled by the interplay of neural crest cell-intrinsic factors and instructive cues from the surrounding gut mesenchyme. However, postnatal ENS development occurs in a different context, which is characterized by the presence of microbiota and an extensive immune System, suggesting an important role of these factors on Enteric neural circuit formation and function. Initial reports confirm this idea while further studies in this area promise new insights into ENS physiology and pathophysiology.
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heterogeneity and phenotypic plasticity of glial cells in the mammalian Enteric Nervous System
Glia, 2015Co-Authors: Werend Boesmans, Reena Lasrado, Pieter Vanden Berghe, Vassilis PachnisAbstract:Enteric glial cells are vital for the autonomic control of gastrointestinal homeostasis by the Enteric Nervous System. Several different functions have been assigned to Enteric glial cells but whether these are performed by specialized subtypes with a distinctive phenotype and function remains elusive. We used Mosaic Analysis with Double Markers and inducible lineage tracing to characterize the morphology and dynamic molecular marker expression of Enteric GLIA in the myEnteric plexus. Functional analysis in individually identified Enteric glia was performed by Ca2+ imaging. Our experiments have identified four morphologically distinct subpopulations of Enteric glia in the gastrointestinal tract of adult mice. Marker expression analysis showed that the majority of glia in the myEnteric plexus co-express glial fibrillary acidic protein (GFAP), S100β, and Sox10. However, a considerable fraction (up to 80%) of glia outside the myEnteric ganglia, did not label for these markers. Lineage tracing experiments suggest that these alternative combinations of markers reflect dynamic gene regulation rather than lineage restrictions. At the functional level, the three myEnteric glia subtypes can be distinguished by their differential response to adenosine triphosphate. Together, our studies reveal extensive heterogeneity and phenotypic plasticity of Enteric glial cells and set a framework for further investigations aimed at deciphering their role in digestive function and disease. GLIA 2015;63:229–241
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glial cells in the mouse Enteric Nervous System can undergo neurogenesis in response to injury
Journal of Clinical Investigation, 2011Co-Authors: Catia Laranjeira, Pieter Vanden Berghe, Katarina Sandgren, Nicoletta Kessaris, William D Richardson, Alexandre J Potocnik, Vassilis PachnisAbstract:The Enteric Nervous System (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of the ENS can be identified in the adult intestine using clonal cultures and in vivo transplantation assays. The identity of these neurogenic precursors in the adult gut and their relationship to the embryonic progenitors of the ENS are currently unknown. Using genetic fate mapping, we here demonstrate that mouse neural crest cells marked by SRY box–containing gene 10 (Sox10) generate the neuronal and glial lineages of Enteric ganglia. Most neurons originated from progenitors residing in the gut during mid-gestation. Afterward, Enteric neurogenesis was reduced, and it ceased between 1 and 3 months of postnatal life. Sox10-expressing cells present in the myEnteric plexus of adult mice expressed glial markers, and we found no evidence that these cells participated in neurogenesis under steady-state conditions. However, they retained neurogenic potential, as they were capable of generating neurons with characteristics of Enteric neurons in culture. Furthermore, Enteric glia gave rise to neurons in vivo in response to chemical injury to the Enteric ganglia. Our results indicate that despite the absence of constitutive neurogenesis in the adult gut, Enteric glia maintain limited neurogenic potential, which can be activated by tissue dissociation or injury.
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Enteric Nervous System development and hirschsprung s disease advances in genetic and stem cell studies
Nature Reviews Neuroscience, 2007Co-Authors: Tiffany A Heanue, Vassilis PachnisAbstract:The Enteric Nervous System (ENS) has been explored by developmental neurobiologists and medical researchers for decades. Whereas developmental biologists have been unravelling the molecular mechanisms underlying the migration, proliferation and differentiation of the neural crest derivatives that give rise to the ENS, human geneticists have been uncovering the genetic basis for diseases of the ENS, notably Hirschsprung's disease. Here we discuss the exciting recent advances, including novel transgenic and genetic tools, a broadening range of model organisms, and the pursuit of ENS stem cells as a therapeutic tool, that are bringing these fields closer together.
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maintenance of mammalian Enteric Nervous System progenitors by sox10 and endothelin 3 signalling
Development, 2006Co-Authors: Nadege Bondurand, Dipa Natarajan, Amanda J Barlow, Nikhil Thapar, Vassilis PachnisAbstract:The transcriptional regulator SOX10 and the signalling molecule endothelin 3 have important roles in the development of the mammalian Enteric Nervous System (ENS). Using a clonal cell culture System, we show that SOX10 inhibits overt neuronal and glial differentiation of multilineage ENS progenitor cells (EPCs), without interfering with their neurogenic commitment. We also demonstrate that endothelin 3 inhibits reversibly the commitment and differentiation of EPCs along the neurogenic and gliogenic lineages, suggesting a role for this factor in the maintenance of multilineage ENS progenitors. Consistent with such a role, the proportion of Sox10-expressing progenitors in the total population of Enteric neural crest cells is reduced in the gut of endothelin 3-deficient embryos. This reduction may be related to the requirement of endothelin signalling for the proliferation of ENS progenitors. The dependence of ENS progenitors on endothelin 3 is more pronounced at the migratory front of Enteric neural crest cells, which is associated with relatively high levels of endothelin 3 mRNA. Our findings indicate that SOX10 and endothelin 3 have a crucial role in the maintenance of multilineage Enteric Nervous System progenitors.
Nadege Bondurand - One of the best experts on this subject based on the ideXlab platform.
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news from the endothelin 3 ednrb signaling pathway role during Enteric Nervous System development and involvement in neural crest associated disorders
Developmental Biology, 2018Co-Authors: Nadege Bondurand, Sylvie Dufour, Veronique PingaultAbstract:Abstract The endothelin System is a vertebrate-specific innovation with important roles in regulating the cardiovascular System and renal and pulmonary processes, as well as the development of the vertebrate-specific neural crest cell population and its derivatives. This System is comprised of three structurally similar 21-amino acid peptides that bind and activate two G-protein coupled receptors. In 1994, knockouts of the Edn3 and Ednrb genes revealed their crucial function during development of the Enteric Nervous System and melanocytes, two neural-crest derivatives. Since then, human and mouse genetics, combined with cellular and developmental studies, have helped to unravel the role of this signaling pathway during development and adulthood. In this review, we will summarize the known functions of the EDN3/EDNRB pathway during neural crest development, with a specific focus on recent scientific advances, and the Enteric Nervous System in normal and pathological conditions.
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maintenance of mammalian Enteric Nervous System progenitors by sox10 and endothelin 3 signalling
Development, 2006Co-Authors: Nadege Bondurand, Dipa Natarajan, Amanda J Barlow, Nikhil Thapar, Vassilis PachnisAbstract:The transcriptional regulator SOX10 and the signalling molecule endothelin 3 have important roles in the development of the mammalian Enteric Nervous System (ENS). Using a clonal cell culture System, we show that SOX10 inhibits overt neuronal and glial differentiation of multilineage ENS progenitor cells (EPCs), without interfering with their neurogenic commitment. We also demonstrate that endothelin 3 inhibits reversibly the commitment and differentiation of EPCs along the neurogenic and gliogenic lineages, suggesting a role for this factor in the maintenance of multilineage ENS progenitors. Consistent with such a role, the proportion of Sox10-expressing progenitors in the total population of Enteric neural crest cells is reduced in the gut of endothelin 3-deficient embryos. This reduction may be related to the requirement of endothelin signalling for the proliferation of ENS progenitors. The dependence of ENS progenitors on endothelin 3 is more pronounced at the migratory front of Enteric neural crest cells, which is associated with relatively high levels of endothelin 3 mRNA. Our findings indicate that SOX10 and endothelin 3 have a crucial role in the maintenance of multilineage Enteric Nervous System progenitors.
Nick J Spencer - One of the best experts on this subject based on the ideXlab platform.
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Long range synchronization within the Enteric Nervous System underlies propulsion along the large intestine in mice
'Springer Science and Business Media LLC', 2021Co-Authors: Nick J Spencer, Lee Travis, Lukasz Wiklendt, Marcello Costa, Timothy J. Hibberd, Simon J. Brookes, Phil Dinning, David A. Wattchow, Julian SorensenAbstract:Nick Spencer et al. made simultaneous multi-site electrophysiological recordings with video imaging of colonic wall movements from ex vivo mouse colon, in order to correlate propulsion of content with underlying electrical signals from the smooth muscle. Their results demonstrate that excitatory and inhibitory junction potentials are synchronized in both the proximal and distal colon, suggesting that the Enteric Nervous System network communicates over a longer range than previously expected
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Enteric Nervous System sensory transduction neural circuits and gastrointestinal motility
Nature Reviews Gastroenterology & Hepatology, 2020Co-Authors: Nick J Spencer, Hongzhen HuAbstract:The gastrointestinal tract is the only internal organ to have evolved with its own independent Nervous System, known as the Enteric Nervous System (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central Nervous System have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of Enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut–brain axis. The Enteric Nervous System (ENS) is essential for life and controls the function of the gastrointestinal tract. Here, an overview of sensory transduction and neural circuits in the ENS is provided, yielding insights into the generation of gastrointestinal motility.
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Enteric Nervous System sensory transduction neural circuits and gastrointestinal motility
Nature Reviews Gastroenterology & Hepatology, 2020Co-Authors: Nick J SpencerAbstract:The gastrointestinal tract is the only internal organ to have evolved with its own independent Nervous System, known as the Enteric Nervous System (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central Nervous System have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of Enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut-brain axis.
Allan M Goldstein - One of the best experts on this subject based on the ideXlab platform.
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white paper on guidelines concerning Enteric Nervous System stem cell therapy for Enteric neuropathies
Developmental Biology, 2016Co-Authors: Alan J Burns, Allan M Goldstein, Karlherbert Schafer, Donald F Newgreen, Lincon A Stamp, Marco Metzger, Ryo Hotta, Heather M Young, Peter W AndrewsAbstract:Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the Enteric Nervous System (ENS) of the gastrointestinal tract (so-called Enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
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sonic hedgehog controls Enteric Nervous System development by patterning the extracellular matrix
Journal of Cell Science, 2016Co-Authors: Nandor Nagy, Ryo Hotta, Csilla Barad, Hannah K Graham, Lily S Cheng, Nora Fejszak, Allan M GoldsteinAbstract:The Enteric Nervous System (ENS) develops from neural crest cells that migrate along the intestine, differentiate into neurons and glia, and pattern into two plexuses within the gut wall. Inductive interactions between epithelium and mesenchyme regulate gut development, but the influence of these interactions on ENS development is unknown. Epithelial-mesenchymal recombinations were constructed using avian hindgut mesenchyme and non-intestinal epithelium from the bursa of Fabricius. These recombinations led to abnormally large and ectopically positioned ganglia. We hypothesized that sonic hedgehog (Shh), a secreted intestinal epithelial protein not expressed in the bursa, mediates this effect. Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in large, ectopic ganglia adjacent to the epithelium. Shh overexpression, achieved in ovo using Shh-encoding retrovirus and in organ culture using recombinant protein, led to intestinal aganglionosis. Shh strongly induced the expression of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulfate proteoglycans that are known to be inhibitory to neural crest cell migration. Shh also inhibited Enteric neural crest-derived cell (ENCC) proliferation, promoted neuronal differentiation, and reduced expression of Gdnf, a key regulator of ENS formation. Ptc1 and Ptc2 were not expressed by ENCCs, and migration of isolated ENCCs was not inhibited by Shh protein. These results suggest that epithelial-derived Shh acts indirectly on the developing ENS by regulating the composition of the intestinal microenvironment.
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pelvic plexus contributes ganglion cells to the hindgut Enteric Nervous System
Developmental Dynamics, 2007Co-Authors: Nandor Nagy, Katherine C Brewer, Olive Mwizerwa, Allan M GoldsteinAbstract:The hindgut Enteric Nervous System (ENS) contains cells originating from vagal and sacral neural crest. In avians, the sacral crest gives rise to the nerve of Remak (NoR) and pelvic plexus. Whereas the NoR has been suggested to serve as the source of sacral crest-derived cells to the gut, the contribution of the pelvic ganglia is unknown. The purpose of this study was to test the hypothesis that the pelvic ganglia contribute ganglion cells to the hindgut ENS. We observed that the quail pelvic plexus develops from neural crest-derived cells that aggregate around the cloaca at embryonic day 5. Using chick–quail tissue recombinations, we found that hindgut grafts did not contain Enteric ganglia unless the pelvic plexus was included. Neurofibers extended from the NoR into the intestine, but no ganglion cell contribution from the NoR was identified. These results demonstrate that the pelvic plexus, and not the NoR, serves as the staging area for sacral crest-derived cells to enter the avian hindgut, confirming the evolutionary conservation of this important embryologic process. Developmental Dynamics 236:73–83, 2007. © 2006 Wiley-Liss, Inc.
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Enteric Nervous System patterning in the avian hindgut
Developmental Dynamics, 2004Co-Authors: Adele M Doyle, Drucilla J Roberts, Allan M GoldsteinAbstract:The Enteric Nervous System (ENS) is principally derived from vagal and sacral neural crest cells that migrate throughout the gastrointestinal tract before differentiating into neurons and glia. These cells form two concentric rings of ganglia and regulate intestinal motility, absorption, and secretion. Abnormalities of ENS development can lead to disorders of intestinal function, including Hirschsprung's disease. These disorders are generally limited to the distal hindgut, suggesting unique features to development of this region. This study characterized the normal spatiotemporal development of the ENS within the avian hindgut. Neural crest cells begin to populate the hindgut at E8, with patterning of both plexuses complete by embryonic day 9. Crest-derived cells arrive in the submucosal layer before the myEnteric layer, as well as differentiate to a neuronal phenotype first. The cloaca demonstrates a unique pattern, characterized by a disorganized myEnteric plexus and a flattened nerve of Remak. Detailed understanding of normal avian hindgut ENS development will allow better utilization of this model System to study abnormalities of the intestinal Nervous System. Developmental Dynamics 229:708–712, 2004 © 2004 Wiley-Liss, Inc.
Veronique Pingault - One of the best experts on this subject based on the ideXlab platform.
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news from the endothelin 3 ednrb signaling pathway role during Enteric Nervous System development and involvement in neural crest associated disorders
Developmental Biology, 2018Co-Authors: Nadege Bondurand, Sylvie Dufour, Veronique PingaultAbstract:Abstract The endothelin System is a vertebrate-specific innovation with important roles in regulating the cardiovascular System and renal and pulmonary processes, as well as the development of the vertebrate-specific neural crest cell population and its derivatives. This System is comprised of three structurally similar 21-amino acid peptides that bind and activate two G-protein coupled receptors. In 1994, knockouts of the Edn3 and Ednrb genes revealed their crucial function during development of the Enteric Nervous System and melanocytes, two neural-crest derivatives. Since then, human and mouse genetics, combined with cellular and developmental studies, have helped to unravel the role of this signaling pathway during development and adulthood. In this review, we will summarize the known functions of the EDN3/EDNRB pathway during neural crest development, with a specific focus on recent scientific advances, and the Enteric Nervous System in normal and pathological conditions.