Enteric Nervous System: Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)Hirschsprung Disease: Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.Myenteric Plexus: One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38)Submucous Plexus: One of two ganglionated neural networks which together form the enteric nervous system. The submucous (Meissner's) plexus is in the connective tissue of the submucosa. Its neurons innervate the epithelium, blood vessels, endocrine cells, other submucosal ganglia, and myenteric ganglia, and play an important role in regulating ion and water transport. (From FASEB J 1989;3:127-38)Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Nervous System: The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)Gastrointestinal Tract: Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).Proto-Oncogene Proteins c-ret: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.Gastrointestinal Motility: The motor activity of the GASTROINTESTINAL TRACT.Digestive System: A group of organs stretching from the MOUTH to the ANUS, serving to breakdown foods, assimilate nutrients, and eliminate waste. In humans, the digestive system includes the GASTROINTESTINAL TRACT and the accessory glands (LIVER; BILIARY TRACT; PANCREAS).Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.SOXE Transcription Factors: A subclass of closely-related SOX transcription factors. Members of this subfamily have been implicated in regulating the differentiation of OLIGODENDROCYTES during neural crest formation and in CHONDROGENESIS.Endothelin-3: A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63)Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neuroglia: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.Glial Cell Line-Derived Neurotrophic Factor: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized CONNECTIVE TISSUE located outside the CENTRAL NERVOUS SYSTEM.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Glial Cell Line-Derived Neurotrophic Factor Receptors: A family of GLYCOSYLPHOSPHATIDYLINOSITOL-anchored cell surface receptors that are specific for GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTORS. They form a multi-component receptor complex with PROTO-ONCOGENE PROTEIN C-RET and regulate a variety of intracellular SIGNAL TRANSDUCTION PATHWAYS in conjunction with c-ret protein.Quail: Common name for two distinct groups of BIRDS in the order GALLIFORMES: the New World or American quails of the family Odontophoridae and the Old World quails in the genus COTURNIX, family Phasianidae.Digestive System Physiological Phenomena: Properties and processes of the DIGESTIVE SYSTEM as a whole or of any of its parts.Megacolon: Dilatation of the COLON, often to alarming dimensions. There are various types of megacolon including congenital megacolon in HIRSCHSPRUNG DISEASE, idiopathic megacolon in CONSTIPATION, and TOXIC MEGACOLON.Vasoactive Intestinal Peptide: A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).Serotonin 5-HT4 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.Peristalsis: A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Interstitial Cells of Cajal: c-Kit positive cells related to SMOOTH MUSCLE CELLS that are intercalated between the autonomic nerves and the effector smooth muscle cells of the GASTROINTESTINAL TRACT. Different phenotypic classes play roles as pacemakers, mediators of neural inputs, and mechanosensors.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Intestinal Pseudo-Obstruction: A type of ILEUS, a functional not mechanical obstruction of the INTESTINES. This syndrome is caused by a large number of disorders involving the smooth muscles (MUSCLE, SMOOTH) or the NERVOUS SYSTEM.Neurofilament Proteins: Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)Jejunum: The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.High Mobility Group Proteins: A family of low-molecular weight, non-histone proteins found in chromatin.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Ileus: A condition caused by the lack of intestinal PERISTALSIS or INTESTINAL MOTILITY without any mechanical obstruction. This interference of the flow of INTESTINAL CONTENTS often leads to INTESTINAL OBSTRUCTION. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced.Celiac Plexus: A complex network of nerve fibers including sympathetic and parasympathetic efferents and visceral afferents. The celiac plexus is the largest of the autonomic plexuses and is located in the abdomen surrounding the celiac and superior mesenteric arteries.Intestine, Large: A segment of the LOWER GASTROINTESTINAL TRACT that includes the CECUM; the COLON; and the RECTUM.Nitrergic Neurons: Nerve cells where transmission is mediated by NITRIC OXIDE.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Central Nervous System Neoplasms: Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Receptors, Serotonin, 5-HT4: A subtype of G-protein-coupled SEROTONIN receptors that preferentially couple to GS STIMULATORY G-PROTEINS resulting in increased intracellular CYCLIC AMP. Several isoforms of the receptor exist due to ALTERNATIVE SPLICING of its mRNA.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Coturnix: A genus of BIRDS in the family Phasianidae, order GALLIFORMES, containing the common European and other Old World QUAIL.Ubiquitin Thiolesterase: A thioester hydrolase which acts on esters formed between thiols such as DITHIOTHREITOL or GLUTATHIONE and the C-terminal glycine residue of UBIQUITIN.Nerve Tissue ProteinsNeurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Receptor, Endothelin B: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.Choline O-Acetyltransferase: An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC A genus of sphinx or hawk moths of the family Sphingidae. These insects are used in molecular biology studies during all stages of their life cycle.Autonomic Nervous System: The ENTERIC NERVOUS SYSTEM; PARASYMPATHETIC NERVOUS SYSTEM; and SYMPATHETIC NERVOUS SYSTEM taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the CENTRAL NERVOUS SYSTEM, especially the HYPOTHALAMUS and the SOLITARY NUCLEUS, which receive information relayed from VISCERAL AFFERENTS.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Gastrointestinal Diseases: Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.Hexamethonium: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.Mice, Inbred C57BLStomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the ESOPHAGUS and the beginning of the DUODENUM.NADPH Dehydrogenase: A flavoprotein that reversibly oxidizes NADPH to NADP and a reduced acceptor. EC 2: A calbindin protein that is differentially expressed in distinct populations of NEURONS throughout the vertebrate and invertebrate NERVOUS SYSTEM, and modulates intrinsic neuronal excitability and influences LONG-TERM POTENTIATION. It is also found in LUNG, TESTIS, OVARY, KIDNEY, and BREAST, and is expressed in many tumor types found in these tissues. It is often used as an immunohistochemical marker for MESOTHELIOMA.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Irritable Bowel Syndrome: A disorder with chronic or recurrent colonic symptoms without a clearcut etiology. This condition is characterized by chronic or recurrent ABDOMINAL PAIN, bloating, MUCUS in FECES, and an erratic disturbance of DEFECATION.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Ganglia, Autonomic: Clusters of neurons and their processes in the autonomic nervous system. In the autonomic ganglia, the preganglionic fibers from the central nervous system synapse onto the neurons whose axons are the postganglionic fibers innervating target organs. The ganglia also contain intrinsic neurons and supporting cells and preganglionic fibers passing through to other ganglia.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Nervous System Physiological Phenomena: Characteristic properties and processes of the NERVOUS SYSTEM as a whole or with reference to the peripheral or the CENTRAL NERVOUS SYSTEM.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Neurturin: A glial cell line-derived neurotrophic factor ligand that is specific for the GFRA2 RECEPTOR. Neurturin is essential for the development of specific postganglionic parasympathetic NEURONS.Gastroparesis: Chronic delayed gastric emptying. Gastroparesis may be caused by motor dysfunction or paralysis of STOMACH muscles or may be associated with other systemic diseases such as DIABETES MELLITUS.Nitric Oxide Synthase Type I: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.Myoelectric Complex, Migrating: A pattern of gastrointestinal muscle contraction and depolarizing myoelectric activity that moves from the stomach to the ILEOCECAL VALVE at regular frequency during the interdigestive period. The complex and its accompanying motor activity periodically cleanse the bowel of interdigestive secretion and debris in preparation for the next meal.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Neuropeptides: Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Gastric Emptying: The evacuation of food from the stomach into the duodenum.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Body Patterning: The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.Hu Paraneoplastic Encephalomyelitis Antigens: A family of RNA-binding proteins that are homologues of ELAV protein, Drosophila. They were initially identified in humans as the targets of autoantibodies in patients with PARANEOPLASTIC ENCEPHALOMYELITIS. They are thought to regulate GENE EXPRESSION at the post-transcriptional level.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.Nervous System Neoplasms: Benign and malignant neoplastic processes arising from or involving components of the central, peripheral, and autonomic nervous systems, cranial nerves, and meninges. Included in this category are primary and metastatic nervous system neoplasms.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.

Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. (1/604)

The terminal colon is aganglionic in mice lacking endothelin-3 or its receptor, endothelin B. To analyze the effects of endothelin-3/endothelin B on the differentiation of enteric neurons, E11-13 mouse gut was dissociated, and positive and negative immunoselection with antibodies to p75(NTR )were used to isolate neural crest- and non-crest-derived cells. mRNA encoding endothelin B was present in both the crest-and non-crest-derived cells, but that encoding preproendothelin-3 was detected only in the non-crest-derived population. The crest- and non-crest-derived cells were exposed in vitro to endothelin-3, IRL 1620 (an endothelin B agonist), and/or BQ 788 (an endothelin B antagonist). Neurons and glia developed only in cultures of crest-derived cells, and did so even when endothelin-3 was absent and BQ 788 was present. Endothelin-3 inhibited neuronal development, an effect that was mimicked by IRL 1620 and blocked by BQ 788. Endothelin-3 failed to stimulate the incorporation of [3H]thymidine or bromodeoxyuridine. Smooth muscle development in non-crest-derived cell cultures was promoted by endothelin-3 and inhibited by BQ 788. In contrast, transcription of laminin alpha1, a smooth muscle-derived promoter of neuronal development, was inhibited by endothelin-3, but promoted by BQ 788. Neurons did not develop in explants of the terminal bowel of E12 ls/ls (endothelin-3-deficient) mice, but could be induced to do so by endothelin-3 if a source of neural precursors was present. We suggest that endothelin-3/endothelin B normally prevents the premature differentiation of crest-derived precursors migrating to and within the fetal bowel, enabling the precursor population to persist long enough to finish colonizing the bowel.  (+info)

IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system. (2/604)

Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1beta and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1beta or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1beta was suppressed by the natural IL-1beta human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1beta or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.  (+info)

Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. (3/604)

BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease.  (+info)

Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. (4/604)

RET is a member of the receptor tyrosine kinase (RTK) superfamily, which can transduce signalling by glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) in cultured cells. In order to determine whether in addition to being sufficient, RET is also necessary for signalling by these growth factors, we studied the response to GDNF and NTN of primary neuronal cultures (peripheral sensory and central dopaminergic neurons) derived from wild-type and RET-deficient mice. Our experiments show that absence of a functional RET receptor abrogates the biological responses of neuronal cells to both GDNF and NTN. Despite the established role of the RET signal transduction pathway in the development of the mammalian enteric nervous system (ENS), very little is known regarding its cellular mechanism(s) of action. Here, we have studied the effects of GDNF and NTN on cultures of neural crest (NC)-derived cells isolated from the gut of rat embryos. Our findings suggest that GDNF and NTN promote the survival of enteric neurons as well as the survival, proliferation and differentiation of multipotential ENS progenitors present in the gut of E12.5-13.5 rat embryos. However, the effects of these growth factors are stage-specific, since similar ENS cultures established from later stage embryos (E14. 5-15.5), show markedly diminished response to GDNF and NTN. To examine whether the in vitro effects of RET activation reflect the in vivo function(s) of this receptor, the extent of programmed cell death was examined in the gut of wild-type and RET-deficient mouse embryos by TUNEL histochemistry. Our experiments show that a subpopulation of enteric NC undergoes apoptotic cell death specifically in the foregut of embryos lacking the RET receptor. We suggest that normal function of the RET RTK is required in vivo during early stages of ENS histogenesis for the survival of undifferentiated enteric NC and their derivatives.  (+info)

Peptidyl inhibitors of shaker-type Kv1 channels elicit twitches in guinea pig ileum by blocking kv1.1 at enteric nervous system and enhancing acetylcholine release. (5/604)

Potent and selective peptidyl blockers of the Shaker-type (Kv1) voltage-gated potassium channels were used to determine the role of these channels in regulating the spontaneous motility of smooth muscle preparations. Margatoxin (MgTX), kaliotoxin, and agitoxin-2 at 1 to 10 nM and agitoxin-1 at 50 to 100 nM induce twitches in guinea pig ileum strips. These twitches are abolished by tetrodotoxin (TTX, 0.5 microM), atropine (1 microM), hexamethonium (10 microM), or nifedipine (0.1 microM). It is proposed that blockade of Kv1 channels by MgTX, kaliotoxin, or the agitoxins increases excitability of intramural nerve plexuses in the ileum, promoting release of acetylcholine from excitatory motor nerve terminals. This, in turn, leads to Ca2+-dependent action potentials and twitching of the muscle fibers. MgTX does not induce twitches in several other guinea pig and/or rat vascular, genitourinary, or gastrointestinal smooth muscles, although small increases in spontaneous myogenic activity may be seen in detrusor muscle exposed to >30 nM MgTX. This effect is not reversed by TTX or atropine. The TTX- and atropine-sensitive twitches of guinea pig ileum are also induced by nanomolar concentrations of alpha-dendrotoxin, a selective blocker of Shaker Kv1.1 and 1.2 subtypes, or stichodactylatoxin, a peptide isolated from sea anemone that displays high affinity for Kv1.1 and 1.3, but not by charybdotoxin, which blocks Kv1.2 and 1.3 but not 1.1. The data taken together suggest that high-affinity blockade of Kv1.1 underlies the ability of MgTX, kaliotoxin, agitoxin-1, agitoxin-2, alpha-dendrotoxin, and stichodactylatoxin to elicit TTX-sensitive twitches in guinea pig ileum.  (+info)

Immune-epithelial interactions in host defense. (6/604)

Over the past 15 years, it has become very clear that the immune system can have profound effects on epithelial function. Acute immune-mediated changes in epithelial physiology are beneficial to host defense against enteric pathogens. For example, ion secretion washes out noxious luminal contents and increased permeability allows phagocytic cells and antibodies to enter the gut lumen. However, ongoing immune activation results in chronic effects that may be pathophysiologic. Responses are mediated by soluble immune mediators that act directly on the epithelium, or indirectly via nerves that also serve to amplify the epithelial response. Here, we will review some of the recent advances that have been made in the field of immunophysiology. The effect of mast cells on transport functions of the epithelium will be reviewed, with emphasis on the consequence of interactions between mast cells and nerves. The use of in vitro coculture systems has recently provided considerable information on the effects of neutrophils, eosinophils, monocytes, and lymphocytes on epithelial functions; the contribution of each immunocyte will be highlighted. Finally, we will describe evidence for the active participation of the epithelium in mucosal immune activation, including pathogen or cytokine induced epithelial cytokine synthesis or secretion and adhesion molecule expression.  (+info)

A role for fasciclin II in the guidance of neuronal migration. (7/604)

The insect cell adhesion receptor fasciclin II is expressed by specific subsets of neural and non-neural cells during embryogenesis and has been shown to control growth cone motility and axonal fasciculation. Here we demonstrate a role for fasciclin II in the guidance of migratory neurons. In the developing enteric nervous system of the moth Manduca sexta, an identified set of neurons (the EP cells) undergoes a stereotyped sequence of migration along the visceral muscle bands of the midgut prior to their differentiation. Probes specific for Manduca fasciclin II show that while the EP cells express fasciclin II throughout embryogenesis, their muscle band pathways express fasciclin II only during the migratory period. Manipulations of fasciclin II in embryonic culture using blocking antibodies, recombinant fasciclin II fragments, and enzymatic removal of glycosyl phosphatidylinositol-linked fasciclin II produced concentration-dependent reductions in the extent of EP cell migration. These results support a novel role for fasciclin II, indicating that this homophilic adhesion molecule is required for the promotion or guidance of neuronal migration.  (+info)

Fundamentals of neurogastroenterology. (8/604)

Current concepts and basic principles of neurogastroenterology in relation to functional gastrointestinal disorders are reviewed. Neurogastroenterology is emphasized as a new and advancing subspecialty of clinical gastroenterology and digestive science. As such, it embraces the investigative sciences dealing with functions, malfunctions, and malformations in the brain and spinal cord, and the sympathetic, parasympathetic and enteric divisions of the autonomic innervation of the digestive tract. Somatomotor systems are included insofar as pharyngeal phases of swallowing and pelvic floor involvement in defecation, continence, and pelvic pain are concerned. Inclusion of basic physiology of smooth muscle, mucosal epithelium, and the enteric immune system in the neurogastroenterologic domain relates to requirements for compatibility with neural control mechanisms. Psychologic and psychiatric relations to functional gastrointestinal disorders are included because they are significant components of neurogastroenterology, especially in relation to projections of discomfort and pain to the digestive tract.  (+info)

  • Within the adult enteric nervous system (ENS) there is a population of neural stem cells (NSCs) that appear to proliferate in vitro following dissociation. (queensu.ca)
  • Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system , DEVELOPMENTAL BIOLOGY 293: (1) pp. 203-217. (doktori.hu)
  • Concomitantly with colonization of the gastrointestinal tract and maturation of the mucosal immune system, the ENS undergoes extensive development during the early postnatal life ( 14 ). (s4me.info)
  • Allied with neurophysiological research are studies of paracrine interactions between the ENS and the enteric immune system. (osu.edu)
  • In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. (edu.au)
  • 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. (inserm.fr)
  • 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. (inserm.fr)
  • 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. (inserm.fr)
  • Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production. (doktori.hu)
  • Immunophenotypic characterization of enteric neural crest cells in the developing avian colorectum. (doktori.hu)
  • Enteric nervous system development: A crest cell's journey from neural tube to colon , SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2017: p. (doktori.hu)
  • Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix. (doktori.hu)
  • A bird's eye view of enteric nervous system development: Lessons from the avian embryo , PEDIATRIC RESEARCH 64: (4) pp. 326-333. (doktori.hu)
  • We used the Genetic Analysis Workshop 15 Problem 1 data set to search for expression phenotype quantitative trait loci in a highly selected group of genes with a supposedly correlated role in the development of the enteric nervous system. (beds.ac.uk)
  • Here we observed that germ-free mice have an immature enteric nervous system (ENS) that is normalized upon colonization with a normal microbiota. (s4me.info)
  • Pelvic plexus contributes ganglion cells to the hindgut enteric nervous system , DEVELOPMENTAL DYNAMICS 236: (1) pp. 73-83. (doktori.hu)
  • This region is particularly interesting because a susceptibility locus for Hirschsprung disease, a disease characterized by enteric malformation, was previously mapped to 9q31. (beds.ac.uk)
  • Over the last few years there have been huge advances made in our understanding of the interactions between the brain and the gut the enteric nervous system this book is particularly relevant in the understanding diagnosis and management of irritable bowel syndrome the most common functional disorder of the bowel. (pafisurabaya.org)
  • These temporal differences in the timing of the last mitosis for precursors that give rise to specific neuron classes suggest that the timing and intensity of trophic factor expression may critically determine the ratio of neuron subtypes within the ENS by altering the proliferation of precursors determined to become specific types of enteric neurons. (jneurosci.org)
  • In humans aberrant development of the enteric nervous system (ENS) manifest as motility disorders. (ebscohost.com)
  • 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. (inserm.fr)
  • Development of the enteric nervous system in the moth. (elsevier.com)
  • The mammalian enteric nervous system is derived from neural crest cells which invade the foregut and hindgut mesenchyme. (nih.gov)
  • It has been established that signalling molecules produced by the mesenchyme of the gut wall play a critical role in the development of the mammalian enteric nervous system. (nih.gov)
  • Differentiation studies of the enteric neurospheres showed that especially ciliary neurotrophic factor (CNTF) increased the number of enteric neurones (PGP positive), while the amount of HNK-1 precursor cells decreased under the influence of all tested neurotrophins but GDNF. (nih.gov)
  • Glial fibrillary acidic protein (GFAP) is expressed in astrocytes, but also expressed outside of the central nervous system. (lenus.ie)
  • We hypothesized that severe injury would increase expression of glial fibrillary acidic protein (GFAP), a marker of enteric glial activation. (physiology.org)
  • To perform these activities, there are many enteric neuron subtypes with distinct transmitter phenotypes, neurite extension patterns, electrophysiology, and function ( Furness, 2000 ). (jneurosci.org)
  • Therefore, I hypothesize that DLX1 and DLX2 are essential for differentiation of specific subtypes of enteric neurons, consistent with the role of these proteins in the developing CNS. (grantome.com)
  • Although these enteric precursors and other components of the neuromuscular apparatus (eg, smooth muscle cells, interstitial cells of Cajal [ICC]) are appropriately arranged by weeks 12 to 14 of human development, the first coordinated gut motility patterns do not occur until approximately birth. (lww.com)
  • Furthermore, to ensure harmony in ENS regulation of smooth muscle movement in the gut, the actions of the enteric neurons must be in concert with other cells type resident in the organ, including the interstitial cells of Cajal, which are responsible for providing pacemaker activity to the gut wall and facilitate the interactions between motor neurones and smooth muscle cells. (projmed.com)
  • 160,000 single nuclei, 831 human enteric neurons and 431 Interstitial Cells of Cajal (ICC) were identified. (biologists.com)
  • To our knowledge, there is no other documented long term change in the responsiveness of enteric neurones and thus no other candidate mechanism for inducing hyper-reactivity within the enteric nervous system. (bmj.com)
  • The neural apparatus is composed of a large number of enteric neurones that can be identified according to their location, neurochemistry, shape, projections, proportions, connections, and function. (bmj.com)
  • After intensive research from several laboratories over the past two decades, a full description of all functional classes of enteric neurones has been recently achieved in the guinea pig small intestine (fig 1 ). (bmj.com)
  • Intrinsic primary afferent neurones appear to differ in the intestines of large and small animals in terms of their chemical coding, distribution over enteric neural networks, electrophysiological behaviour and synaptic properties. (umn.edu)
  • Inflammatory bowel disease causes structural and functional alterations in the enteric nervous system (ENS). (queensu.ca)
  • Over the last few years there have been huge advances made in our understanding of the interactions between the brain and the gut the enteric nervous system this book is particularly relevant in the understanding diagnosis and management of irritable bowel syndrome the most common functional disorder of the bowel. (pafisurabaya.org)
  • Pathophysiology of the enteric nervous system a basis for understanding functional diseases by robin spiller editor david grundy editor 27 oct 2004 hardcover books amazonca. (pafisurabaya.org)
  • Zebrafish: an exciting model for investigating the spatio-temporal pattern of enteric nervous system development. (lenus.ie)
  • Ret signaling is critical for formation of the enteric nervous system (ENS) because Ret activation promotes ENS precursor survival, proliferation, and migration and provides trophic support for mature enteric neurons. (jneurosci.org)
  • Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. (biologists.org)
  • The enteric nervous system (ENS) plays a pivotal role in inflammatory and nociceptive processes. (hindawi.com)
  • Nervous system that is involved primarily with the internal regulation of the gustatory processes. (zfin.org)
  • 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. (inserm.fr)
  • The brain also interacts with an extended nervous system outside the brain that controls body metabolic processes such as respiration, heart rate, temperature, and digestion. (mhmedical.com)