Epithelial fusion is mediated by a partial epithelial-mesenchymal transition

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Epithelial fusion is crucial for organ development, but the cellular mechanisms driving it are unclear.
• Previous studies focused on neural tube and palatal closure, leaving other systems less understood.
• The cellular transitions enabling epithelial fusion remain a significant knowledge gap.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms of epithelial fusion during chick otic vesicle closure.
• To identify and characterize the specific cell types involved in mediating this morphogenetic process.
• To understand the role of epithelial-to-mesenchymal transition (EMT) in epithelial fusion.

Main Methods:

• Microdissection of chick otic vesicle tissues.
• Transcriptomic profiling to identify distinct cell populations.
• CRISPR-Cas9 gene editing to assess gene function.
• Immunofluorescence microscopy to analyze cell morphology and protein localization.

Main Results:

• Identified a transient population of otic edge (OE) cells at the epithelial interface with reduced polarity and altered cell junctions.
• OE cells exhibit characteristics of a partial epithelial-to-mesenchymal transition (EMT) phenotype, including high sphericity and lack of basal contact.
• Transcriptomic analysis revealed OE cells are transcriptionally distinct, enriched for EMT regulators, ECM remodeling genes, and WNT pathway components.
• Knockdown of Grhl2 or Sp8 transcription factors disrupted cell morphology, junctional integrity, and epithelial segregation.

Conclusions:

• Epithelial fusion requires a regulated, hybrid EMT state that balances junctional plasticity with tissue cohesion.
• Fusion-competent epithelial cells actively modulate their shape, polarity, adhesion, and genetic identity during morphogenesis.
• This study provides novel insights into the cellular basis of epithelial fusion, essential for understanding organ development and congenital defects.