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1.
BMC Biol ; 12: 25, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24674670

RESUMO

BACKGROUND: Abnormalities in pyloric development or in contractile function of the pylorus cause reflux of duodenal contents into the stomach and increase the risk of gastric metaplasia and cancer. Abnormalities of the pyloric region are also linked to congenital defects such as the relatively common neonatal hypertrophic pyloric stenosis, and primary duodenogastric reflux. Therefore, understanding pyloric development is of great clinical relevance. Here, we investigated the role of the LIM homeodomain transcription factor Isl1 in pyloric development. RESULTS: Examination of Isl1 expression in developing mouse stomach by immunohistochemistry, whole mount in situ hybridization and real-time quantitative PCR demonstrated that Isl1 is highly expressed in developing mouse stomach, principally in the smooth muscle layer of the pylorus. Isl1 expression was also examined by immunofluorescence in human hypertrophic pyloric stenosis where the majority of smooth muscle cells were found to express Isl1. Isl1 function in embryonic stomach development was investigated utilizing a tamoxifen-inducible Isl1 knockout mouse model. Isl1 deficiency led to nearly complete absence of the pyloric outer longitudinal muscle layer at embryonic day 18.5, which is consistent with Gata3 null mouse phenotype. Chromatin immunoprecipitation, luciferase assays, and electrophoretic mobility shift assays revealed that Isl1 ensures normal pyloric development by directly targeting Gata3. CONCLUSIONS: This study demonstrates that the Isl1-Gata3 transcription regulatory axis is essential for normal pyloric development. These findings are highly clinically relevant and may help to better understand pathways leading to pyloric disease.


Assuntos
Fator de Transcrição GATA3/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Piloro/metabolismo , Fatores de Transcrição/metabolismo , Actinas/metabolismo , Animais , Apoptose , Proliferação de Células , Citocinas , Elementos Facilitadores Genéticos/genética , Feminino , Fator de Transcrição GATA3/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas com Homeodomínio LIM/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Músculos/patologia , Piloro/anormalidades , Piloro/embriologia , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica
2.
Gastroenterology ; 146(1): 157-165.e10, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24120474

RESUMO

BACKGROUND & AIMS: Infantile hypertrophic pyloric stenosis is a common birth anomaly characterized by obstruction of the pyloric lumen. A genome-wide association study implicated NKX2-5, which encodes a transcription factor that is expressed in embryonic heart and pylorus, in the pathogenesis of infantile hypertrophic pyloric stenosis. However, the function of the NKX2-5 in pyloric smooth muscle development has not been examined directly. We investigated the pattern of Nkx2-5 during the course of murine pyloric sphincter development and examined coexpression of Nkx2-5 with Gata3 and Sox9-other transcription factors with pyloric-specific mesenchymal expression. We also assessed pyloric sphincter development in mice with disruption of Nkx2-5 or Gata3. METHODS: We used immunofluorescence analysis to compare levels of NKX2-5, GATA3, and SOX9 in different regions of smooth muscle cells. Pyloric development was assessed in mice with conditional or germline deletion of Nkx2-5 or Gata3, respectively. RESULTS: Gata3, Nkx2-5, and Sox9 are coexpressed in differentiating smooth muscle cells of a distinct fascicle of the pyloric outer longitudinal muscle. Expansion of this fascicle coincides with development of the pyloric sphincter. Disruption of Nkx2-5 or Gata3 causes severe hypoplasia of this fascicle and alters pyloric muscle shape. Although expression of Sox9 requires Nkx2-5 and Gata3, there is no apparent hierarchical relationship between Nkx2-5 and Gata3 during pyloric outer longitudinal muscle development. CONCLUSIONS: Nkx2-5 and Gata3 are independently required for the development of a pyloric outer longitudinal muscle fascicle, which is required for pyloric sphincter morphogenesis in mice. These data indicate that regulatory changes that alter Nkx2-5 or Gata3 expression could contribute to pathogenesis of infantile hypertrophic pyloric stenosis.


Assuntos
Fator de Transcrição GATA3/metabolismo , Proteínas de Homeodomínio/metabolismo , Desenvolvimento Muscular/fisiologia , Músculo Liso/embriologia , Miócitos de Músculo Liso/metabolismo , Piloro/embriologia , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição/metabolismo , Animais , Imunofluorescência , Proteína Homeobox Nkx-2.5 , Camundongos , Músculo Liso/metabolismo , Piloro/metabolismo
3.
Pediatr Radiol ; 43(12): 1656-61, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23832020

RESUMO

Pyloric atresia is an uncommon congenital gastric outlet obstruction, accounting for only 1% of gastrointestinal atresias. Up to 55% of cases have associated anomalies, the most common of which is epidermolysis bullosa. Fetal MRI findings of the epidermolysis bullosa-pyloric atresia association have not been previously reported. We present a case of this association diagnosed by prenatal MRI with corroborative postnatal imaging and surgical findings.


Assuntos
Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/embriologia , Obstrução da Saída Gástrica/diagnóstico , Obstrução da Saída Gástrica/embriologia , Imageamento por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos , Piloro/anormalidades , Humanos , Recém-Nascido , Piloro/embriologia , Estatística como Assunto
4.
Gene Expr Patterns ; 13(8): 287-92, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23727297

RESUMO

Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach.


Assuntos
Proteínas Aviárias/genética , Colo/metabolismo , Genes Homeobox , Moela das Aves/metabolismo , Fatores de Transcrição/genética , Animais , Proteínas Aviárias/metabolismo , Embrião de Galinha , Colo/citologia , Colo/embriologia , Mucosa Gástrica/embriologia , Mucosa Gástrica/metabolismo , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Moela das Aves/citologia , Moela das Aves/embriologia , Mucosa Intestinal/embriologia , Mucosa Intestinal/metabolismo , Miócitos de Músculo Liso/metabolismo , Especificidade de Órgãos , Piloro/citologia , Piloro/embriologia , Piloro/metabolismo , Reto/citologia , Reto/embriologia , Reto/metabolismo , Fatores de Transcrição/metabolismo
5.
Prog Mol Biol Transl Sci ; 96: 35-62, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21075339

RESUMO

The discrete organs that comprise the gastrointestinal tract (esophagus, stomach, small intestine, and large intestine) arise embryonically by regional differentiation of a single tube that is initially morphologically similar along its length. Regional organ differentiation programs, for example, for stomach or intestine, involve signaling cross-talk between epithelium and mesenchyme and result in the formation of precise boundaries between organs, across which dramatic differences in both morphology and gene expression are seen. The pylorus is a unique area of the gut tube because it not only marks an important organ boundary in the tubular gut (the stomach/intestinal boundary) but is also the hub for the development of multiple accessory organs (liver, pancreas, gall bladder, and spleen). This chapter examines: (a) our current understanding of the molecular and morphogenic processes that underlie the generation of the dramatic epithelial tissue boundary that compartmentalizes stomach and intestine; (b) the tissue interactions that promote development of the accessory organs in this area; and (c) the molecular interactions that specify patterning of the pyloric sphincter. Though the focus here is primarily on the mouse as a model organism, the molecular underpinnings of organ patterning near the pylorus are shared by chick and frog. Thus, further study of these conserved developmental programs could potentially shed light on the mechanisms underlying human pyloric malformations such as infantile hypertrophic pyloric stenosis.


Assuntos
Morfogênese , Especificidade de Órgãos , Piloro/embriologia , Animais , Padronização Corporal , Endoderma/citologia , Humanos , Mesoderma/citologia , Piloro/citologia
6.
Dev Dyn ; 238(12): 3205-17, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19877272

RESUMO

In the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus, and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4 gamma, Creb3l3, and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan.


Assuntos
Desenvolvimento Fetal/genética , Mucosa Intestinal/embriologia , Intestinos/embriologia , Piloro/embriologia , Piloro/metabolismo , Estômago/embriologia , Animais , Embrião de Mamíferos , Feminino , Desenvolvimento Fetal/fisiologia , Mucosa Gástrica/metabolismo , Perfilação da Expressão Gênica , Idade Gestacional , Mucosa Intestinal/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Óperon Lac/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , Gravidez , Proteína GLI1 em Dedos de Zinco
7.
Dev Biol ; 334(2): 409-17, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19660448

RESUMO

The functional activity of Six2, a member of the so/Six family of homeodomain-containing transcription factors, is required during mammalian kidney organogenesis. We have now determined that Six2 activity is also necessary for the formation of the pyloric sphincter, the functional gate at the stomach-duodenum junction that inhibits duodenogastric reflux. Our data reveal that several genes known to be important for pyloric sphincter formation in the chick (e.g., Bmp4, Bmpr1b, Nkx2.5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse.


Assuntos
Proteínas Fetais/fisiologia , Redes Reguladoras de Genes/fisiologia , Proteínas de Homeodomínio/fisiologia , Piloro/embriologia , Fatores de Transcrição/fisiologia , Actinas/biossíntese , Animais , Proteína Morfogenética Óssea 4/biossíntese , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/biossíntese , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/fisiologia , Citocinas , Refluxo Duodenogástrico/embriologia , Proteínas Fetais/biossíntese , Proteínas Fetais/genética , Mucosa Gástrica/embriologia , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes/genética , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Mesoderma/metabolismo , Camundongos , Músculo Liso/metabolismo , Organogênese , Piloro/anormalidades , Fatores de Transcrição SOX9/biossíntese , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/fisiologia , Estômago/embriologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/biossíntese , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
8.
Surg Radiol Anat ; 31(5): 335-41, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19107317

RESUMO

OBJECTIVE: The objective of this study was to explore the localization of the pylorus, its macroscopic and microscopic development and relationship with neighboring structures. MATERIALS AND METHODS: The study is carried out on 160 human fetuses aged between 9 and 40 weeks of gestation. Abdomen was divided into four quadrants by horizontal and vertical planes passing through the umbilicus. Topographical localization of the pylorus in reference to these quadrants and its distance were determined. Pylorus was divided into pre-pyloric, pyloric, and post-pyloric regions. Starting from the pre-pyloric end, serial sections spanning whole pyloric part were obtained. Wall thickness, the thickness of the muscular coat were measured under light microscope using sections stained with hematoxylin eosin. Sections with the thickest muscular coat were considered as the region where pyloric sphincter was. FINDINGS: Pylorus was located in the right upper quadrant, on the median plane and in the left upper quadrant. There was a significant relation between the thickness of the muscular coat in the stomach, duodenum and the pyloric region and gestational age. In the region of the pyloric sphincter, the rate of increase in the thickness of the muscular coat was higher in the first and the first half of the second trimesters than term fetuses. CONCLUSION: We believe that data obtained in the present study will contribute to the assessment of development of the pyloric region in intra-uterine cases.


Assuntos
Desenvolvimento Fetal , Piloro/embriologia , Feminino , Humanos , Masculino , Valores de Referência
9.
Gastroenterology ; 130(4): 1233-44, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16618415

RESUMO

BACKGROUND & AIMS: Fibroblast growth factors (Fgfs) and their receptors (Fgfrs) are important intercellular signaling molecules that are essential to mammalian embryonic development. The signaling pathways between endoderm-derived gastric epithelium and the surrounding mesenchyme are largely unknown; however, the developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its main ligand, Fgf10, suggest that they may be strong candidates. Mice lacking either component (Fgfr2b-/- or Fgf10-/-) were examined to determine the role of Fgfr2b-mediated signaling during gastric organogenesis. METHODS: Stomachs from embryonic day 13.5-18.5 Fgfr2b-/-, Fgf10-/-, and wild-type littermates were collected and analyzed by conventional histology, immunohistochemistry, in situ hybridization, and electron microscopy. RESULTS: Fgfr2b-/- and Fgf10-/- fetuses had stomachs smaller than wild-type, consisting of relatively proportionate forestomach but disproportionately reduced glandular stomach, the mucosa of which has low cytoarchitectural complexity with a spiral arrangement of large mucosal folds. During mid to late fetal stages (embryonic day 15.5-18.5), epithelial differentiation to mucous and chief cell lineages was rudimentary, with no expression of several early cytodifferentiation markers including GATA4, GATA6, and H+/K+-adenosine triphosphatase and abnormal expression of members of the hedgehog family of signaling molecules. CONCLUSIONS: Fgfr2b and Fgf10 are part of a signaling network with Sonic hedgehog and Indian hedgehog that are essential to anterior-posterior and radial patterning in gastric development.


Assuntos
Fator 10 de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/fisiologia , Estômago/embriologia , Animais , Padronização Corporal/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/fisiologia , Mucosa Gástrica/embriologia , Camundongos , Camundongos Knockout , Células Parietais Gástricas/citologia , Piloro/embriologia , Distribuição Tecidual , Fatores de Transcrição/metabolismo
10.
Dev Biol ; 279(2): 481-90, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15733673

RESUMO

The organs of the digestive tract are specified by coordinated signaling between the endoderm and mesoderm during development. These epithelial-mesenchymal interactions lead to the organ-specific morphogenesis and differentiation of regions along the gut tube. In this paper, we show that in the chick, the SRY-related transcription factor Sox9 is a marker for the posterior gizzard. Viral misexpression of Sox9 in the gizzard mesoderm is sufficient to specify epithelium characteristic of the pyloric sphincter. Sox9 expression is normally limited to the region of the posterior gizzard under the regulation of BMP signaling from the adjacent midgut. Misexpression of an activated form of BMPR1b in the gizzard upregulates Sox9 expression, while the BMP antagonist noggin down-regulates Sox9 expression in the gizzard mesoderm. Previously, Nkx2.5 was identified as a marker for the mesoderm of the pyloric sphincter. As with Sox9, BMP signaling appears to regulate Nkx2.5 and its ability to determine the pyloric epithelium. Despite these similarities, our evidence suggests that Sox9 and Nkx2.5 are regulated independently by BMP signaling, and act coordinately to specify the pyloric sphincter.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Epitélio/embriologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas de Homeodomínio/metabolismo , Piloro/anatomia & histologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Animais , Biomarcadores , Embrião de Galinha , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Moela das Aves/anatomia & histologia , Moela das Aves/embriologia , Moela das Aves/metabolismo , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Homeodomínio/genética , Hibridização In Situ , Piloro/embriologia , Retroviridae/genética , Retroviridae/metabolismo , Fatores de Transcrição SOX9 , Fatores de Transcrição/genética
11.
Development ; 131(15): 3795-804, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15240557

RESUMO

Gastrointestinal (GI) development is highly conserved across vertebrates. Although several transcription factors and morphogenic proteins are involved in the molecular controls of GI development, the interplay between these factors is not fully understood. We report herein the expression pattern of Sox9 during GI development, and provide evidence that it functions, in part, to define the pyloric sphincter epithelium. SOX9 is expressed in the endoderm of the GI tract (with the exclusion of the gizzard) and its derivate organs, the lung and pancreas. Moreover, SOX9 is also expressed at the mesoderm of the pyloric sphincter, a structure that demarcates the gizzard from the duodenum. Using retroviral misexpression technique, we show that Sox9 expression in the pyloric sphincter is under the control of the BMP signaling pathway, known to play a key role in the development of this structure. By misexpressing SOX9 in the mesoderm of the gizzard, we show that SOX9 is able to transdifferentiate the adjacent gizzard epithelium into pyloric sphincter-like epithelium through the control of mesodermal-epithelial signals mediated in part by Gremlin (a modulator of the BMP pathway). Our results suggest that SOX9 is necessary and sufficient to specify the pyloric sphincter epithelial properties.


Assuntos
Epitélio/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Grupo de Alta Mobilidade/metabolismo , Mesoderma/fisiologia , Músculo Liso/embriologia , Transdução de Sinais/fisiologia , Estômago/embriologia , Fatores de Transcrição/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Embrião de Galinha , Epitélio/anatomia & histologia , Epitélio/metabolismo , Mucosa Gástrica/metabolismo , Moela das Aves/citologia , Moela das Aves/embriologia , Moela das Aves/metabolismo , Proteínas de Grupo de Alta Mobilidade/genética , Humanos , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mesoderma/citologia , Morfogênese , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/metabolismo , Piloro/anatomia & histologia , Piloro/embriologia , Piloro/metabolismo , Fatores de Transcrição SOX9 , Estômago/anatomia & histologia , Fatores de Transcrição/genética
13.
Dev Dyn ; 224(1): 90-102, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11984877

RESUMO

In the adult gastrointestinal tract, the morphologic borders between esophagus and stomach and between stomach and small intestine are literally one cell thick. The patterning mechanisms that underlie the development of these sharp regional divisions from a once continuous endodermal tube are still obscure. In the embryonic endoderm of the developing gut, region-specific expression of certain genes (e.g., intestine-specific expression of the actin bundling protein villin) can be detected as early as 9.0 days post coitum, although the morphologic differentiation of the gut epithelium proper does not begin until 4 to 5 days later. By using a mouse model in which a beta-galactosidase marker has been inserted into the endogenous villin locus, we examined the development of the stomach/intestinal (pyloric) border during gut organogenesis. The data indicate that the border is not sharp from the outset. Rather, the initial border region is characterized by a decreasing gradient of villin/beta-galactosidase expression that extends into the distal stomach. A sharp epithelial border of villin/beta-galactosidase expression appears abruptly at day 16 and is further refined over the next 3 weeks to form the distinct one-cell-thick border characteristic of the adult. These results indicate that an important previously unrecognized patterning event occurs in the gut epithelium at 16 days; this event may define an epithelial compartment boundary between the stomach and the intestine. The villin/beta-galactosidase mouse model characterized here provides an excellent substrate with which to further dissect the mechanisms involved in this patterning process.


Assuntos
Proteínas de Transporte/metabolismo , Células Epiteliais/fisiologia , Mucosa Gástrica/embriologia , Mucosa Intestinal/embriologia , Proteínas dos Microfilamentos/metabolismo , Piloro/embriologia , Animais , Padronização Corporal , Encéfalo/citologia , Encéfalo/embriologia , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte/genética , Cóclea/citologia , Cóclea/embriologia , Células Epiteliais/citologia , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , Genes Reporter , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Proteínas dos Microfilamentos/genética , Gravidez , Piloro/citologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Sistema Urogenital/embriologia , Sistema Urogenital/metabolismo , beta-Galactosidase/metabolismo
14.
Ann R Coll Surg Engl ; 82(6): 371-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11103151

RESUMO

Infantile hypertrophic pyloric stenosis is the most common cause for urgent abdominal surgery in infancy. The aetiology of the condition is unknown. The ontogeny of the innervation and structure of the normal infant pylorus is unknown. A variety of differing histological features have been attributed to this condition and a number of animal models have been described. The histological changes in the human condition and those in the animal models have not been quantified and statistically verified. Thus, precise comparisons cannot be made. Immunohistochemistry was the principal technique employed in this study. Using this technique, the ontogeny and structure of the normal infant pylorus have been documented. The morphological and immunohistochemical changes underlying infantile hypertrophic pyloric stenosis have been quantified for the first time and compared with the quantified changes in natural and experimental animal models of this condition.


Assuntos
Estenose Pilórica/etiologia , Piloro/embriologia , Piloro/inervação , Animais , Modelos Animais de Doenças , Cães , Desenvolvimento Embrionário e Fetal , Feminino , Humanos , Hipertrofia/etiologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Lactente , Recém-Nascido , Masculino , Camundongos , Óxido Nítrico Sintase/metabolismo , Estenose Pilórica/metabolismo , Estenose Pilórica/patologia , Peptídeo Intestinal Vasoativo/metabolismo
15.
Development ; 127(17): 3671-81, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10934012

RESUMO

Patterning of the gut into morphologically distinct regions results from the appropriate factors being expressed in strict spatial and temporal patterns to assign cells their fates in development. Often, the boundaries of gene expression early in development correspond to delineations between different regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard. Ectopic BMP4 in the gizzard caused a thinning of the muscularis. To understand this phenotype we examined the expression of the receptors transducing BMP signaling during gut development. We find that the BMP receptors are differentially expressed in distinct regions of the chicken embryonic gut. By using constitutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expressed. We show that the mesodermal thinning seen upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in proliferation within the gizzard mesoderm. The mesodermal thinning is characterized by a disorganization and lack of differentiation of smooth muscle in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4. This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard. We also find that Nkx2.5 is necessary and sufficient for establishing aspects of pyloric sphincter differentiation.


Assuntos
Padronização Corporal/fisiologia , Proteínas Morfogenéticas Ósseas/fisiologia , Sistema Digestório/embriologia , Moela das Aves/embriologia , Proteínas de Homeodomínio/fisiologia , Transdução de Sinais , Fatores de Transcrição , Proteínas de Xenopus , Animais , Apoptose , Proteína Morfogenética Óssea 4 , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Divisão Celular , Embrião de Galinha , Perfilação da Expressão Gênica , Moela das Aves/metabolismo , Moela das Aves/fisiologia , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mesoderma/fisiologia , Piloro/embriologia
16.
Neurogastroenterol Motil ; 11(5): 375-92, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10520169

RESUMO

Networks of interstitial cells of Cajal (ICC) in the myenteric plexus (Myp) or circular muscle (CM) function as pacemakers for gastrointestinal slow waves. ICC in contact with muscle and closely associated with nerves in the CM may mediate inhibitory neurotransmission. We wondered if ICC in Myp and CM and their connections are immature at birth and mature first in the proximal gut in association with nerves. Tissues from lower esophageal sphincter (LES), pylorus (PYL), small intestine (SI) and colon (CO) of 18 term fetal dogs taken from six females were fixed and prepared for ultrastructural examination and studied. Ganglia were present where expected in the Myp and submucous plexus (SMP). ICC cells were present in the Myp of PYL, SI and CO and appeared to have normal relationships to the outer border of CM as in adults. ICC in CM were found associated with nerves in the LES and in PYL, but not in SI or CO. However, axons in CM were everywhere usually free of glial covering, indicating ongoing migration or development. No organized deep muscular plexus (DMP) in SI or submuscular plexus (SP) in colon was present. Visible gap junctions were absent everywhere except for very rare ones between circular muscle cells. We conclude that at birth the neural and ICC networks of CM are more immature in intestine and colon than in oesophagus and stomach. Development of nerve and ICC of CM in oesophagus and stomach apparently precedes that in the remaining gut. However networks in these regions have not achieved adult organization and ICC and smooth muscle cells are anatomically poorly coupled. These findings suggest the reasons that gut motility at birth will not be adult in pattern are because ICC, nerve and muscle control systems are not fully differentiated. Further developmental delays in ICC and nerve maturation could have serious consequences for feeding of infant animals.


Assuntos
Feto/fisiologia , Motilidade Gastrointestinal/fisiologia , Plexo Mientérico/embriologia , Animais , Relógios Biológicos/fisiologia , Colo/embriologia , Colo/inervação , Colo/ultraestrutura , Cães , Esôfago/embriologia , Esôfago/inervação , Esôfago/ultraestrutura , Feminino , Feto/ultraestrutura , Junções Comunicantes/fisiologia , Íleo/embriologia , Íleo/inervação , Íleo/ultraestrutura , Microscopia Eletrônica , Plexo Mientérico/citologia , Plexo Mientérico/fisiologia , Gravidez , Piloro/embriologia , Piloro/inervação , Piloro/ultraestrutura
17.
J Pediatr Surg ; 33(4): 613-8, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9574762

RESUMO

PURPOSE: The aim of this study was to document the vagal innervation and expression of neuropeptides, neuronal nitric oxide synthase (nNOS), and neural cell adhesion molecule (NCAM) in the neuromuscular system of the developing human pylorus. METHODS: Specimens of human pylorus (n = 54; age range, 8 weeks' gestation to 6 months postnatal) were studied. Vagal innervation was determined by Dil autofluorescence. A wide range of neuropeptides, NCAM, and the neural isoform of NOS were examined by immunohistochemistry. RESULTS: Vagal innervation was first recognized in the myenteric plexus in the 12-week-old fetus as was vasoactive intestinal polypeptide (VIP) expression. Neuropeptides were present from 8 weeks' gestation and appeared to be expressed progressively from the adventitia toward the mucosa and showed an adultlike profile by 23 weeks' gestation. A craniocaudal pattern of expression was noted for VIP and nNOS. Alpha smooth muscle actin was expressed by muscle fibers of the muscularis propria from 8 weeks and the muscularis mucosae by 14 weeks. All the isoforms of NCAM examined were expressed from 8 weeks in the muscularis propria and by 12 weeks in the submucosa. CONCLUSION: The expression of the antigens studied correlated with the gestational age and development of the pylorus.


Assuntos
Piloro/inervação , Nervo Vago/embriologia , Desenvolvimento Embrionário e Fetal , Feminino , Feto/inervação , Mucosa Gástrica/embriologia , Mucosa Gástrica/inervação , Idade Gestacional , Humanos , Recém-Nascido , Músculo Liso/embriologia , Músculo Liso/inervação , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Neuropeptídeos/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo I , Gravidez , Piloro/embriologia , Peptídeo Intestinal Vasoativo/metabolismo
18.
J Anat ; 193 ( Pt 4): 587-97, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10029192

RESUMO

The mucosubstances in the epithelium lining the segment from gizzard to duodenum during development of the chick embryo was studied histochemically using monoclonal antibodies against gizzard mucus and lectins, with attention to the regional differentiation of the epithelium in this segment. The anterior limit of epithelial CdxA mRNA expression detected by in situ hybridisation, which served as the position of the gizzard-duodenal boundary, was clearly found from d 3. Granules positive for some antibodies or lectins were found in the region ranging from the posterior part of the gizzard to the duodenum at d 3, which was followed by an increase in the number of granules and a gradual enlargement of the granule-positive area to the anterior part of the gizzard over 4-6 d. From d 4, the epithelia of the gizzard body and of the pyloric or duodenal region came to be differently stained with some antibodies or lectins. From d 10, each region showed a specific pattern of staining. The epithelia of the gizzard body and pyloric region contained abundant mucus granules with a different staining pattern. In the duodenum the number of stained granules was low except in occasional goblet cells. Thus the epithelia of the gizzard body, pyloric region and duodenum may produce different mucosubstances and the regional differentiation in these epithelia may start at rather early stages soon after the formation of digestive tube.


Assuntos
Embrião de Galinha/crescimento & desenvolvimento , Mucosa Intestinal/embriologia , Muco/metabolismo , Animais , Anticorpos Monoclonais , Embrião de Galinha/metabolismo , Duodeno/química , Duodeno/embriologia , Duodeno/metabolismo , Idade Gestacional , Moela das Aves/química , Moela das Aves/embriologia , Moela das Aves/metabolismo , Histocitoquímica , Imuno-Histoquímica , Mucosa Intestinal/química , Mucosa Intestinal/metabolismo , Lectinas , Muco/imunologia , Piloro/química , Piloro/embriologia , Piloro/metabolismo
20.
Anat Embryol (Berl) ; 182(6): 605-10, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2075918

RESUMO

The times of first appearance and the distribution of APP- and glucagon-immunoreactive cells have been established in the embryonic chick gut between 11 days of incubation and hatching. These immunoreactive cell types appeared for the first time at 13 days of incubation, APP-immunoreactive cells in the duodenum and upper ileum and glucagon-immunoreactive cells in the proventriculus and duodenum. At 14 days, APP-immunoreactive cells were detected in the proventriculus and lower ileum and glucagon-immunoreactive cells in the pyloric region, upper and lower ileum. Thereafter both APP- and glucagon-immunoreactive cells increased in frequency until the numbers at hatching were approximated, APP-immunoreactive cells at 19 days and glucagon immunoreactive cells at 17 1/2 days of incubation. No APP- or glucagon-immunoreactive cells were found in the gizzard, caecum or rectum at any of the selected stages examined. When these types of endocrine cells first appeared, the surface epithelium of the gastrointestinal tract was relatively undifferentiated. A few glands were present in the proventriculus only, at this stage. Thereafter immunoreactive cells of both types were found in the glandular epithelium of the proventriculus, pyloric region and small intestine soon after morphogenesis had begun.


Assuntos
Mucosa Gástrica/metabolismo , Glucagon/metabolismo , Mucosa Intestinal/metabolismo , Polipeptídeo Pancreático/metabolismo , Fatores Etários , Animais , Anticorpos/imunologia , Diferenciação Celular/fisiologia , Embrião de Galinha , Duodeno/embriologia , Mucosa Gástrica/embriologia , Glucagon/imunologia , Imuno-Histoquímica , Mucosa Intestinal/embriologia , Polipeptídeo Pancreático/imunologia , Proventrículo/embriologia , Piloro/embriologia
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