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Sonic hedgehog is essential to foregut development

Y Litingtung1, L Lei, H Westphal

  • 1Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2175, USA.

Nature Genetics
|September 10, 1998
PubMed
Summary
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Sonic hedgehog (Shh) is crucial for developing the esophagus, trachea, and lungs. Shh-deficient mice exhibit congenital foregut malformations similar to human conditions, highlighting Shh

Area of Science:

  • Developmental Biology
  • Genetics
  • Medical Research

Background:

  • Congenital foregut malformations affect 1 in 3000 live births.
  • The etiology of human foregut defects remains largely unknown.
  • Sonic hedgehog (Shh) signaling is vital in embryonic development.

Purpose of the Study:

  • To investigate the role of Sonic hedgehog (Shh) in foregut development.
  • To understand the molecular mechanisms underlying congenital foregut malformations.
  • To explore the potential involvement of SHH mutations in human foregut defects.

Main Methods:

  • Utilized a mouse model with targeted deletion of the Sonic hedgehog (Shh) gene.
  • Analyzed embryonic development from embryonic day 9.5.
  • Examined tracheal and lung anomalies, cell death, proliferation, and gene expression in Shh-null mutants.

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Main Results:

  • Shh-null mutant mice displayed oesophageal atresia/stenosis and tracheo-oesophageal fistula.
  • Tracheal and lung anomalies were observed in homozygous Shh-null mice.
  • Lung mesenchyme showed increased cell death, reduced proliferation, and downregulated Shh target genes.

Conclusions:

  • Sonic hedgehog (Shh) is essential for the growth and differentiation of the oesophagus, trachea, and lungs.
  • The study suggests Shh signaling is critical for normal foregut development.
  • Mutations in SHH or its signaling pathway components may contribute to human congenital foregut defects.