title: Perturbed intraepithelial differentiation of corneal epithelium in c-Fos-null mice.
abstract: OBJECTIVE
  AP-1 is a transcription factor that plays a pivotal role in regulating cellular homeostasis and which may modulate the differentiation of corneal epithelial cells. We examined the role of c-Fos in the differentiation of corneal epithelial cells by using c-Fos-deficient (c-fos (-/-)) mice.
  
  
  METHODS
  Ten adult c-fos (-/-) mice and ten control (c-fos (+/-) or c-fos (+/+)) mice were used. The expression patterns of the mRNA and protein of keratin 12 (K12) were determined to examine the differentiation of cornea-type epithelium. To evaluate the intraepithelial differentiation from basal cells to superficial cells, the ultrastructure of the corneal epithelium was studied. We focused on the formation of desmosomes in the superficial, suprabasal, and basal cell layers, and also on the hemidesmosomes. The number of desmosomes in each epithelial layer was statistically analyzed by using an unpaired t test. The expressions of keratin 14 (K14), desmoglein, E-cadherin, occludin, connexin 43, filaggrin, loricrin, and involucrin were examined to analyze epithelial differentiation.
  
  
  RESULTS
  The mRNA and protein of K12 were expressed in the corneal epithelium of c-fos (-/-) and control mice. Ultrastructural observations showed that the number of desmosomes between the basal cells of the corneal epithelia was similar in c-fos (-/-) and control mice. However, there were fewer desmosomes between suprabasal cells and between superficial cells in c-fos (-/-) mice than in control mice. The number of hemidesmosomes in the corneal epithelial cells in c-Fos-null mice was similar to that in control mice. The expressions of the other epithelial cell differentiation markers were not affected by the absence of c-Fos. Ultrastructural observations showed a disarrangement of the corneal epithelium in the c-Fos-null mice.
  
  
  CONCLUSIONS
  The absence of c-Fos disturbs the formation of desmosomes in the superficial layers of the corneal epithelium, suggesting a perturbation of intraepithelial differentiation from the basal epithelial cells to the suprabasal and superficial epithelial cells.
authors: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. yokada@wakayama-med.ac.jp
authors: Yuka
authors: Y
authors: Okada
authors: Emiko
authors: E
authors: Senba
authors: Kumi
authors: K
authors: Shirai
authors: Tekashi
authors: T
authors: Ueyama
authors: Peter
authors: P
authors: Reinach
authors: Shizuya
authors: S
authors: Saika
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019573:Epithelium, Corneal / Q000166:cytology* / Q000648:ultrastructure; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053551:Keratin-12 / Q000235:genetics / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007381:Intermediate Filament Proteins; C507495:KRT12 protein, mouse; D053551:Keratin-12; D053547:Keratin-14; C507446:Krt14 protein, mouse; D008562:Membrane Glycoproteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger