Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Ciliopathies are a group of human diseases stemming from defects in primary cilia, essential organelles for sensing cellular environments.
• Transmembrane protein 107 (TMEM107) localizes to primary cilia and is implicated in ciliopathies like oral-facial-digital syndrome.

Purpose of the Study:

• To investigate the role of Tmem107 in craniofacial development, specifically palate formation, using a Tmem107 knockout mouse model.
• To elucidate the underlying mechanisms of craniofacial abnormalities caused by Tmem107 deficiency.

Main Methods:

• Generation and analysis of Tmem107 knockout (Tmem107-/-) mouse embryos.
• Detailed morphological and skeletal analysis of craniofacial structures.
• Investigation of gene expression patterns (SOX2, SOX9, Shh, Gli1) and primary cilia morphology.

Main Results:

• Tmem107-/- mice exhibited severe craniofacial defects, including cleft lip, exencephaly, and microphthalmia.
• Palate development was impaired, leading to cleft secondary palate due to abnormal mesenchymal proliferation and horizontalization.
• Region-specific alterations in primary cilia morphology and disrupted expression of key developmental genes (SOX2, SOX9, Shh, Gli1) were observed.

Conclusions:

• TMEM107 is essential for normal craniofacial development, particularly palate formation.
• Tmem107 deficiency leads to region-specific primary cilia defects, impacting signaling pathways and causing complex developmental abnormalities.
• These findings highlight TMEM107's critical role in embryonic development and provide insights into ciliopathy pathogenesis.