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

Dev Dyn. 2001 Nov;222(3):471-83. doi: 10.1002/dvdy.1205.

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.

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Cell Division / physiology
  • Chimera
  • Congenital Abnormalities / pathology
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / physiology
  • Embryonic and Fetal Development
  • Eyelids / abnormalities
  • Eyelids / embryology*
  • Hair / abnormalities
  • Hair / embryology
  • Hair / growth & development
  • Hair / pathology
  • Mice / embryology
  • Mice, Inbred Strains
  • Mice, Nude
  • Mice, Transgenic / genetics
  • Mutation / physiology
  • Ploidies
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Receptor Protein-Tyrosine Kinases / deficiency
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / deficiency
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism
  • Receptors, Fibroblast Growth Factor / physiology*
  • Skin / embryology*
  • Skin Abnormalities / embryology
  • Skin Abnormalities / genetics
  • Skin Abnormalities / pathology
  • Skin Transplantation

Substances

  • Receptors, Fibroblast Growth Factor
  • Fgfr2 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2