Proper development of the outer longitudinal smooth muscle of the mouse pylorus requires Nkx2-5 and Gata3

Aaron M. Udager, Ajay Prakash, David A. Saenz, Martina Schinke, Takashi Moriguchi, Patrick Y. Jay, Kim Chew Lim, James Douglas Engel, Deborah L. Gumucio

研究成果: Article査読

16 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)157-165.e10
ジャーナルGastroenterology
146
1
DOI
出版ステータスPublished - 2014 1月

ASJC Scopus subject areas

  • 肝臓学
  • 消化器病学

フィンガープリント

「Proper development of the outer longitudinal smooth muscle of the mouse pylorus requires Nkx2-5 and Gata3」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル