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Expression of Indian Hedgehog, BMP-4 and Noggin in craniosynostosis induced by fetal constraint

Shushan Jacob1, Changshan Wu, Theresa A Freeman

  • 1Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Annals of Plastic Surgery
|January 25, 2007
PubMed

Insights

Fetal constraint reduces Indian Hedgehog (Ihh) and Noggin signaling, impacting bone formation and potentially causing craniosynostosis. Ihh signaling appears crucial for osteogenic cell proliferation in developing cranial sutures.

Area of Science:

  • Developmental Biology
  • Craniofacial Development
  • Molecular Biology

Background:

  • Indian Hedgehog (Ihh), bone morphogenetic protein (BMP), and Noggin are key regulators of bone formation.
  • Craniosynostosis is a condition involving premature fusion of cranial sutures.
  • The molecular mechanisms underlying constraint-induced craniosynostosis are not fully understood.

Purpose of the Study:

  • To investigate the role of Ihh, BMP, and Noggin signaling in craniosynostosis induced by fetal constraint.
  • To examine the expression of key signaling molecules in a mouse model of constraint-induced craniosynostosis.

Main Methods:

  • C57Bl/6 mice underwent cervical cerclage on day 18 of gestation.
  • Pups were harvested 48 and 72 hours post-gestation.
  • Expression of BMP-4, Noggin, Histone H4C, Ihh, Sonic Hedgehog (Shh), and Patched 1 (Ptch1) was analyzed in constrained and control calvariae.

Main Results:

  • Constraint-induced suture fusion was linked to decreased Ihh and Noggin expression.
  • BMP-4 expression was present in both control and constrained sutures.
  • Ptch1 colocalized with Ihh-positive cells, suggesting Ihh regulates Ptch1 in cranial sutures.
  • Histone H4C was preferentially expressed in Ihh-positive cells, indicating Ihh's role in osteogenic cell proliferation.

Conclusions:

  • Ihh and Noggin signaling pathways are implicated in constraint-induced craniosynostosis.
  • Ihh signaling, rather than Shh, appears to regulate Ptch1 expression in cranial suture development.
  • Ihh signaling may control osteogenic cell proliferation at the osteogenic fronts during suture development.

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