Perturbed intraepithelial differentiation of corneal epithelium in c-Fos-null mice.
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.
Okada
Yuka
Y
Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. yokada@wakayama-med.ac.jp
Senba
Emiko
E
Shirai
Kumi
K
Ueyama
Tekashi
T
Reinach
Peter
P
Saika
Shizuya
S
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
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