Exogenous FGF10 can rescue an eye-open at birth phenotype of Fgf10-null mice by activating activin and TGFalpha-EGFR signaling.
Mutant mice deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit an eye-open phenotype at birth. It has previously been shown that FGF10 has a dual role in proliferation and migration during the early and later stages of eyelid development, respectively. To verify the role of FGF10 during eyelid closure, explant culture of Fgf10-null eyelid anlagen was performed, by which it was examined whether or not exogenous FGF10 could rescue the expression of activin betaB and transforming growth factor alpha, known to be required for eyelid closure. We found that the expression of these genes was markedly induced while that of Shh or Ptch1, Ptch2 was not. We also observed the distribution of filamentous actin (F-actin) after FGF10 application in the mutant eyelid explant, finding that the FGF10 protein induced F-actin accumulation. We further examined filopodia of the eyelid leading edge cells, finding the length of the filopodia was significantly reduced in the mutant. These results verify that FGF10 promotes eyelid closure through activating activin and TGFalpha-EGFR signaling.
Tao
Hirotaka
H
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, 2-1 Minami-Jyosanjima, Tokushima 770-8506, Japan.
Ono
Katsuhiko
K
Kurose
Hitomi
H
Noji
Sumihare
S
Ohuchi
Hideyo
H
D000199:Actins / Q000378:metabolism; D028341:Activins / Q000378:metabolism; D000818:Animals; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000378:metabolism; D005143:Eyelids / Q000187:drug effects / Q000196:embryology*; D005260:Female; D005333:Fetus; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D053823:Hedgehog Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010641:Phenotype; D011554:Pseudopodia / Q000648:ultrastructure; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D000199:Actins; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D028341:Activins; D066246:ErbB Receptors