Abstract
Purpose: :
G protein-coupled receptor 48 (GPR48), also known as LGR4, belongs to the leucine-rich G protein coupled receptor family. Mice deficient in GPR48 showed an eye open at birth (EOB) phenotype. In this study, we attempted to clarify the role of GPR48 in eyelid development.
Methods: :
X-gal staining was performed to determine the expression pattern of GPR48 during eyelid development. Histology and scanning electron microscopy analyses were carried out to examine the detailed phenotype of GPR48 null mice. Cell proliferation and apoptosis were assessed by BrdU incorporation and TUNEL assay, respectively. In vitro scratch assay was performed to determine cell motility.
Results: :
GPR48 is highly expressed in the eyelid epithelium and mesenchymal cells of eyelid tips during embryonic development. Deletion of GPR48 led to impairment in embryonic eyelid closure. Detailed analysis revealed that mutant mice exhibited delayed leading edge extension, reduced filopodia formation in eyelid epithelium, and decreased rounded periderm cell formation around eyelid margins. Keratinocyte lacking GPR48 are defective in cell proliferation and migration with reduced F-actin staining in migrating epithelial cells.
Conclusions: :
Inactivation of GPR48 induces the eye open at birth phenotype by reducing epithelial cell proliferation and migration, indicating that GPR48 plays an essential role in eyelid development.
Keywords: eyelid • transgenics/knock-outs • development