Dataset Information

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

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.

SUBMITTER: Udager AM

PROVIDER: S-EPMC3889663 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Udager Aaron M AM Prakash Ajay A Saenz David A DA Schinke Martina M Moriguchi Takashi T Jay Patrick Y PY Lim Kim-Chew KC Engel James Douglas JD Gumucio Deborah L DL

Gastroenterology 20131009 1

<h4>Background & aims</h4>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 c ...[more]

PMID: 24120474

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Dataset Information

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

Background & aims

Methods

Results

Conclusions

Publications

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

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