ADAM17 transactivates EGFR signaling during embryonic eyelid closure

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• ADAM17 is implicated in epidermal growth factor receptor (EGFR) signaling through shedding of membrane-bound ligands.
• ADAM17's broader role in shedding other ligands suggests involvement in multiple molecular pathways.
• The precise function of ADAM17 in embryonic eyelid closure remains to be fully elucidated.

Purpose of the Study:

• To experimentally determine the role of ADAM17 in mammalian embryonic eyelid closure.
• To identify ADAM17-mediated molecular pathways essential for this developmental process.

Main Methods:

• Evaluation of wild-type and Adam17-mutant (woe) mice using histology and microscopy.
• Immunohistochemistry to assess expression of ADAM17, EGFR, and phosphorylated EGFR.
• Cell proliferation, apoptosis, and migration assays (BrdU, TUNEL, scratch assays) were performed.
• Genetic rescue experiments using a hypermorphic Egfr allele were conducted.

Main Results:

• woe mice displayed failed embryonic eyelid closure due to defects in eyelid edge development.
• ADAM17 expression was localized to the eyelid leading edge epithelium and is vital for epithelial cell migration.
• ADAM17 is not involved in proliferation or apoptosis during eyelid closure.
• Phosphorylated EGFR was present in wild-type but absent in woe mice; Egfr rescue normalized eyelid closure and other developmental defects.

Conclusions:

• ADAM17 acts in vivo to transactivate EGFR signaling, which is essential for embryonic eyelid closure.
• This study provides genetic evidence for ADAM17's critical role in regulating EGFR signaling during eyelid development.