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Distinct Involvement of X-Inactivation in Organogenesis.

M Kawasaki1, K Kawasaki1,2, M Fukushima1,3

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

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|March 18, 2026
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Summary

X-inactivation impacts palate and tooth development differently. Mutant cells lacking OFD1 cause cleft palate in all mice, but lead to varied tooth defects due to altered Wnt signaling and cell clustering.

Keywords:
Efnb1Ofd1XCIpalate developmentprimary ciliatooth development

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Area of Science:

  • Developmental Biology
  • Genetics
  • Mammalian Embryogenesis

Background:

  • X-inactivation balances gene expression between sexes.
  • Random X-chromosome inactivation creates mosaicism in females.
  • The role of X-inactivation in craniofacial development is not fully understood.

Purpose of the Study:

  • To investigate the role of X-inactivation in palate and tooth development.
  • To determine the effect of OFD1 (Oculofaciogenital syndrome 1) gene mutation on craniofacial development.

Main Methods:

  • Utilized heterozygous Ofd1 mutant mice (Ofd1fl/WT;Wnt1Cre[HET]).
  • Observed palate and tooth development phenotypes.
  • Analyzed cell behavior and gene expression (EFNB1, Wnt signaling).

Main Results:

  • All Ofd1 mutant mice exhibited cleft palate due to Ofd1 mutant cell accumulation and EFNB1 deficiency.
  • Ofd1 mutant cells accumulated in palatal shelves, causing segregation and cleft palate.
  • Tooth development showed variable phenotypes (extra/absent incisors) linked to Ofd1 mutant cell clusters and impaired Wnt signaling.

Conclusions:

  • X-inactivation plays distinct roles in palate versus tooth development.
  • Ofd1 mutation disrupts palate development uniformly but causes diverse tooth phenotypes.
  • Cell-autonomous effects of X-inactivation contribute to craniofacial developmental anomalies.