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Fig. 8. Proposed model for the function of HB-EGF in leading edge formation during eyelid closure. (A) Before E15.0, the leading edge is still not formed, and HB-EGF expression is not detectable. (B) At E15.0, the leading edge starts to extend, and HB-EGF expression appears at the tip of the leading edge. (C) From E15.0 to E16.0, HB-EGF is constitutively expressed at the tip of the extending leading edge. On the surface of the cells located in this region, ectodomain shedding of proHB-EGF may be mediated by ADAM17 (TACE), allowing sHB-EGF to diffuse throughout the leading edge region. sHB-EGF binds to and activates EGFR and the ERK pathway, resulting in F-actin polymerization and promotion of epithelial sheet migration.





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