Runx1 is involved in the fusion of the primary and the secondary palatal shelves.
Runx1 is expressed in medial edge epithelial (MEE) cells of the palatal shelf. Conditionally rescued Runx1(-/-) mice showed limited clefting in the anterior junction between the primary and the secondary palatal shelves, but not in the junction between the secondary palates. In wild type mice, the fusing epithelial surface exhibited a rounded cobblestone-like appearance, while such cellular prominence was less evident in the Runx1 mutants. We also found that Fgf18 was expressed in the mesenchyme underlying the MEE and that locally applied FGF18 induced ectopic Runx1 expression in the epithelium of the palatal explants, indicating that Runx1 was induced by mesenchymal Fgf18 signaling. On the other hand, unpaired palatal explant cultures revealed the presence of anterior-posterior (A-P) differences in the MEE fates and fusion mechanism. Interestingly, the location of anterior clefting in Runx1 mutants corresponded to the region with different MEE behavior. These data showed a novel function of Runx1 in morphological changes in the MEE cells in palatal fusion, which is, at least in part, regulated by the mesenchymal Fgf signaling via an epithelial-mesenchymal interaction.
Charoenchaikorn
Kesinee
K
Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Suita, Japan.
Yokomizo
Tomomasa
T
Rice
David P
DP
Honjo
Tadashi
T
Matsuzaki
Kiyomi
K
Shintaku
Yuko
Y
Imai
Yuichi
Y
Wakamatsu
Asami
A
Takahashi
Satoru
S
Ito
Yoshiaki
Y
Takano-Yamamoto
Teruko
T
Thesleff
Irma
I
Yamamoto
Masayuki
M
Yamashiro
Takashi
T
D000818:Animals; D002972:Cleft Palate / Q000235:genetics / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D010159:Palate / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D046509:Tissue Culture Techniques
D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors