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Msx1 and Msx2 gene expression is downregulated in the cadmium-induced omphalocele in the chick model

Takashi Doi1, Prem Puri, John Bannigan

  • 1The Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland.

Journal of Pediatric Surgery
|July 13, 2010
PubMed
Abstract

Insights

Cadmium exposure in chick embryos significantly downregulates Msx1 and Msx2 gene expression early in development. This early downregulation of Msx1 and Msx2 may cause the omphalocele birth defect.

Area of Science:

  • Developmental biology
  • Toxicology
  • Genetics

Background:

  • Cadmium (Cd) exposure is known to induce an omphalocele phenotype in chick embryos.
  • The precise molecular mechanisms underlying Cd-induced omphalocele remain unclear.
  • Msx1 and Msx2 genes are crucial for regulating cellular proliferation and differentiation in the developing body wall.

Purpose of the Study:

  • To investigate the hypothesis that cadmium exposure downregulates Msx1 and Msx2 gene expression during critical periods of chick embryogenesis.
  • To explore the role of Msx1 and Msx2 in the development of cadmium-induced omphalocele.

Main Methods:

  • Chick embryos were exposed to cadmium or saline and harvested at 1, 4, and 8 hours post-treatment.
  • Messenger RNA (mRNA) levels of Msx1 and Msx2 were quantified using real-time polymerase chain reaction.
  • Protein expression of Msx1 and Msx2 was examined via immunohistochemistry.

Main Results:

  • A significant decrease in Msx1 and Msx2 mRNA levels was observed at 1 hour post-cadmium exposure compared to controls (P < .01).
  • Immunoreactivity for Msx1 and Msx2 proteins was also markedly reduced at 1 hour in the cadmium-exposed group.
  • No significant differences in gene or protein expression were found at later time-points (4H and 8H).

Conclusions:

  • Early-stage downregulation of Msx1 and Msx2 gene expression by cadmium during embryogenesis is implicated in omphalocele development.
  • Disruption of cellular proliferation and differentiation in the developing body wall likely results from this early gene expression change.
  • Msx1 and Msx2 play a critical role in preventing omphalocele during the narrow window of early embryogenesis.

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