Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning

Initiating as protruding ridges above and below the optic vesicle, the eyel ids of mice grow across the eye and temporarily fuse in fetal life. Mutatio ns of a number of genes disrupt this developmental process and result in a birth defect, "open-eyelids at birth." Here we show that a critical event f or eyelid induction occurs at embryonic day 11.5 (E11.5) when the single ce ll-layered ectoderm in the presumptive eyelid territory increases prolifera tion and undergoes morphologic transition to form cube-shaped epithelial ce lls. Using embryos lacking the Fgfr2 Ig domain III (Fgfr2(Delta III/Delta I II)) generated by tetraploid rescue and chimeric embryo formation approache s, we demonstrate that this event is controlled by Fgfr2 signals as the Fgf r2(Delta III/Delta III) mutation blocks these changes and results in embryo s without eyelids. Fgfr2 and its ligands are differentially expressed in th e ectoderm and underlying mesenchyme and function in a reciprocal interacti ng loop that specifies eyelid development. We also demonstrate that similar defects account for failure of skin formation at early stages. Interesting ly, Fgfr2-independent skin formation occurs at E14.5 mutant embryos, result ing in much thinner, yet well-differentiated epidermis. Notably, mutant ski n remains thin with decreased hair density after transplantation to wild-ty pe recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. Published 2001 Wiley-Liss, Inc.