FGF signalling orchestrates multiple roles during salivary gland branching morphogenesis

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• Organ development relies on intricate form-function relationships established during embryogenesis.
• Epithelial organs like the lung and kidney undergo branching morphogenesis to maximize surface area.
• Fibroblast Growth Factors (FGFs) from the mesenchyme regulate epithelial branching, but downstream pathways remain unclear.

Purpose of the Study:

• To identify molecular players and transcriptional changes downstream of FGF signaling during salivary gland branching morphogenesis.
• To investigate the role of FGF signaling in coordinating epithelial development with vascular and nerve growth.
• To elucidate FGF's function in establishing epithelial architecture and cell fate.

Main Methods:

• Utilized murine salivary gland ex vivo culture for studying branching morphogenesis.
• Compared morphological and transcriptional changes following pharmaceutical inhibition versus genetic deletion of FGF receptors.
• Employed molecular analyses to identify downstream signaling pathways and gene expression changes.

Main Results:

• FGF signaling is essential for coordinating nerve and blood vessel growth with the developing salivary gland epithelium.
• FGF plays a role in forming cell-cell junctions, vital for epithelial integrity.
• FGF signaling via ERK is critical for upregulating cKIT, a marker for mature bud cells, suggesting influence on cell fate.

Conclusions:

• FGF signaling is a multifaceted regulator of salivary gland branching morphogenesis.
• This study reveals FGF's importance in epithelial architecture, vascular coordination, and cell fate determination.
• Identified key downstream molecular events mediated by FGF signaling during gland development.