title: Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning.
abstract: 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.
authors.affiliation: Genetics Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: W
authors.initials: W
authors.lastname: Weinberg
authors.forename: C X
authors.initials: CX
authors.lastname: Deng
mesh_terms: 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
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2