title: The regulation of endogenous retinoic acid level through CYP26B1 is required for elevation of palatal shelves.
abstract: BACKGROUND
  In previous studies, we investigated the effects of excess retinoic acid (RA) during palatogenesis by RA administration to pregnant mice. In the present study, we deleted Cyp26b1, one of the RA-degrading enzymes, to further study the effects of excess RA in the normal developing palate and to understand how endogenous levels of RA are regulated.
  
  
  RESULTS
  Excess RA, due to the absence of Cyp26b1, targets cells in the bend region of the palatal shelves and inhibits their horizontal elevation, leading to cleft palate. An organ culture of Cyp26b1-/- palatal shelves after tongue removal did not rescue the impaired elevation of the palatal shelves. The expression of Fgf10, Bmp2, and Tbx1, important molecules in palatal development, was down-regulated. Cell proliferation was decreased in the bend region of palatal shelves. Tongue muscles were hypoplastic and/or missing in Cyp26b1-/- mice.
  
  
  CONCLUSIONS
  We demonstrated that CYP26B1 is essential during palatogenesis. Excess RA due to the lack of Cyp26b1 suppresses the expression of key regulators of palate development in the bend region, resulting in a failure in the horizontal elevation of the palatal shelves. The regulation of RA signaling through CYP26B1 is also necessary for the development of tongue musculature and for tongue depression.
authors.affiliation: Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. junkookanodr@gmail.com
authors.forename: Junko
authors.initials: J
authors.lastname: Okano
authors.forename: Wataru
authors.initials: W
authors.lastname: Kimura
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Papaionnou
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miura
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.forename: Kohei
authors.initials: K
authors.lastname: Shiota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010159:Palate / Q000196:embryology* / Q000378:metabolism*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase