Septin7 regulates inner ear formation at an early developmental stage

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• Septins are conserved GTP-binding proteins forming complexes vital for cell functions like morphogenesis and apoptosis.
• The inner ear's development involves complex processes including apoptosis and cell fate determination, requiring precise molecular regulation.

Purpose of the Study:

• To investigate the role of Septin 7 (Sept7) in the development and morphogenesis of the mammalian inner ear.
• To determine the impact of early versus late deletion of Sept7 on inner ear development.

Main Methods:

• Utilized a conditional knockout mouse model (Foxg1Cre;Septin7^{floxed/floxed}) to delete Sept7 in the inner ear at embryonic day 9.5 (E9.5).
• Examined inner ear morphology, cell proliferation, and apoptosis at various embryonic stages (E10.5-E15.5).
• Compared results with mice where Sept7 deletion occurred later in development (around E15.5) using Emx2Cre.

Main Results:

• Early Sept7 deletion (E9.5) led to cystic malformations, reduced sensory epithelial cells, and excessive apoptosis in the developing inner ear.
• Mature hair cells were present, but overall inner ear size and sensory epithelial area were compromised.
• Late Sept7 deletion (E15.5) did not cause significant morphological anomalies.

Conclusions:

• SEPT7 plays a critical role in the gross morphogenesis of the inner ear.
• SEPT7 is essential for maintaining the size of the sensory epithelial area, particularly during early developmental stages.
• The timing of Sept7 deletion is crucial, with early loss impacting development more severely than later loss.