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Ift88 is involved in mandibular development.

Atsushi Kitamura1,2, Maiko Kawasaki1,3, Katsushige Kawasaki1,3,4

  • 1Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Journal of Anatomy
|October 29, 2019
PubMed
Summary

Primary cilia, essential for development, impact mandibular bone formation. Deleting the Ift88 protein in mice caused abnormal mandibular bone growth and altered cartilage, partly via Sonic hedgehog signaling.

Keywords:
Hedgehog signalingIft88Meckel's cartilagemandibular bone

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Genetics

Background:

  • Primary cilia are vital cellular organelles involved in signaling pathways crucial for embryonic development.
  • Ciliopathies, diseases arising from primary cilia dysfunction, often manifest with craniofacial abnormalities, including mandibular deformities.
  • The specific role of primary cilia in mandibular development, encompassing chondrogenesis and osteogenesis, remains incompletely understood.

Purpose of the Study:

  • To investigate the function of primary cilia in mandibular development using genetic manipulation in mice.
  • To elucidate the contribution of the ciliary protein Ift88 to chondrogenesis and osteogenesis in the mandible.
  • To explore the relationship between primary cilia function and Sonic hedgehog (Shh) signaling in mandibular morphogenesis.

Main Methods:

  • Generated conditional knockout mice with mesenchymal deletion of the ciliary protein Ift88 (Ift88fl/fl ;Wnt1Cre).
  • Analyzed mandibular morphology, including bone formation and Meckel's cartilage development, in Ift88 mutant mice.
  • Investigated the expression of Hedgehog (Hh) signaling pathway components, including Smoothened (Smo), in the mandibular mesenchyme.

Main Results:

  • Mice lacking Ift88 in the mandibular mesenchyme exhibited ectopic bone formation and modest shortening of the mandible.
  • Meckel's cartilage showed moderate expansion in Ift88 mutant mandibles.
  • Downregulation of Hh signaling was observed in the mesenchyme of Ift88 mutant mandibles, suggesting a role in Shh pathway regulation.

Conclusions:

  • The ciliary protein Ift88 plays a significant role in mandibular chondrogenesis and osteogenesis.
  • Primary cilia regulate mandibular development, in part, through modulation of the Sonic hedgehog signaling pathway.
  • Understanding cilia function in craniofacial development is critical for addressing related congenital anomalies.