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 eyelids of mice grow across the eye and temporarily fuse in fetal life. Mutations 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 for eyelid induction occurs at embryonic day 11.5 (E11.5) when the single cell-layered ectoderm in the presumptive eyelid territory increases proliferation and undergoes morphologic transition to form cube-shaped epithelial cells. Using embryos lacking the Fgfr2 Ig domain III (Fgfr2(DeltaIII/DeltaIII)) generated by tetraploid rescue and chimeric embryo formation approaches, we demonstrate that this event is controlled by Fgfr2 signals as the Fgfr2(DeltaIII/DeltaIII) mutation blocks these changes and results in embryos without eyelids. Fgfr2 and its ligands are differentially expressed in the ectoderm and underlying mesenchyme and function in a reciprocal interacting loop that specifies eyelid development. We also demonstrate that similar defects account for failure of skin formation at early stages. Interestingly, Fgfr2-independent skin formation occurs at E14.5 mutant embryos, resulting in much thinner, yet well-differentiated epidermis. Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning.
Li
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C
Genetics Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Guo
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H
Xu
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Weinberg
W
W
Deng
C X
CX
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002678:Chimera; D000013:Congenital Abnormalities / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005314:Embryonic and Fetal Development; D005143:Eyelids / Q000002:abnormalities / Q000196:embryology*; D006197:Hair / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D051379:Mice / Q000196:embryology; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation / Q000502:physiology; D011003:Ploidies; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000196:embryology*; D012868:Skin Abnormalities / Q000196:embryology / Q000235:genetics / Q000473:pathology; D016038:Skin Transplantation
D017468:Receptors, Fibroblast Growth Factor; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2