Proper development of the outer longitudinal smooth muscle of the mouse pylorus requires Nkx2-5 and Gata3.
Gastroenterology
; 146(1): 157-165.e10, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24120474
ABSTRACT
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.Palavras-chave
BMP; E; ICM; IHPS; Infantile Hypertrophic Pyloric Stenosis; OLM; Primary Duodenogastric Reflux; SRF; Smooth Muscle Development; Sox9; WT; bone morphogenetic protein; embryonic day; infantile hypertrophic pyloric stenosis; inner circular muscle; outer longitudinal muscle; serum response factor; wild type; α-smooth muscle actin; αSMA
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piloro
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Fatores de Transcrição
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Proteínas de Homeodomínio
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Desenvolvimento Muscular
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Miócitos de Músculo Liso
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Fator de Transcrição GATA3
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Fatores de Transcrição SOX9
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Músculo Liso
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article