FGF/FGFR-2(IIIb) signaling is essential for inner ear morphogenesis

Area of Science:

• Developmental Biology
• Genetics
• Otolaryngology

Background:

• Fibroblast Growth Factor 10 (FGF10) and Fibroblast Growth Factor Receptor 2 IIIb (FGFR-2(IIIb)) interactions are essential for organogenesis, particularly budding morphogenesis.
• The specific roles of FGF10 and FGFR-2(IIIb) in inner ear development were not fully understood.

Purpose of the Study:

• To investigate the expression patterns of FGF10 and FGFR-2(IIIb) in the developing inner ear.
• To analyze the inner ear phenotype of mice lacking FGFR-2(IIIb) to determine its necessity for inner ear development.

Main Methods:

• Analysis of FGF10 and FGFR-2(IIIb) mRNA expression patterns in the developing mouse inner ear.
• Generation and analysis of a mouse model with targeted deletion of the FGFR-2(IIIb) isoform.

Main Results:

• FGF10 and FGFR-2(IIIb) exhibited distinct, non-overlapping expression patterns in the early otic epithelium, suggesting intraepithelial paracrine signaling rather than mesenchymal-epithelial signaling.
• FGF10 was localized to presumptive sensory epithelia and neuronal precursors, while FGFR-2(IIIb) was found in the nonsensory epithelium.
• Targeted deletion of FGFR-2(IIIb) led to severe malformations of the cochleovestibular labyrinth, including underdeveloped sensory patches and the cochleovestibular ganglion.

Conclusions:

• FGFR-2(IIIb) signaling is critical for the morphological development of the inner ear.
• Inner ear development relies on intraepithelial paracrine signaling involving FGF10 and FGFR-2(IIIb).
• FGF3 may also play a role in otocyst morphogenesis through FGFR-2(IIIb).