title: Retinoic acid regulates Lhx8 expression via FGF-8b to the upper jaw development of chick embryo.
abstract: Expression of the LIM homeodomain transcription factor Lhx8 is restricted to and up-regulated in the mesenchyme of the upper face prominence before lip fusion. Msx1/2 acts in early development to control cell proliferation and differentiation. Deficiency of these genes is associated with nonsyndromic cleft lip with/without cleft palate. Since retinoid is a potential patterning influence on the developing face, we have examined whether retinoic acid (RA) signaling regulated Lhx8, Msx1 and Msx2 transcription through fibroblast growth factor (FGF) signals in the maxillary prominence. Application of exogenous RA caused severe defects of the maxilla. Citral also induced a specific loss of derivatives from the maxillary prominences by blocking RA synthesis. Real-time RT-PCR and semi-quantitative RT-PCR analysis of the maxillary mesenchyme revealed that the expressions of Lhx8, Msx1 and Msx2 were significantly down-regulated by RA as well as by citral. The downregulated Lhx8 was rescued by combined treatment with FGF-8b, which indicated a downstream of RA signaling. FGF-8b induced up-regulated Lhx8 expression whereas SU5402, a pan-FGF family antagonist, down-regulated and caused defective maxillary morphogenesis and cleft lip. Our data suggest that Lhx8 is regulated by RA signaling through FGF signals and the level window of RA and FGF-8b could control the upper jaw morphogenesis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: bashoudo@naramed-u.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Shimomura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: mkawaka@naramed-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawakami
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, Nara, Japan. Electronic address: okuda@naramed-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuda
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, Nara, Japan. Electronic address: radha815@naramed-u.ac.jp.
authors.forename: Kouko
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, Nara, Japan. Electronic address: morita@naramed-u.ac.jp.
authors.forename: Shoko
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Ophthalmology, Nara Medical University, Nara, Japan. Electronic address: drive19830224@yahoo.co.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nochioka
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: tkirita@naramed-u.ac.jp.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, Nara, Japan. Electronic address: akiow@naramed-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects; D051524:Fibroblast Growth Factor 8 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D007568:Jaw / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051957:MSX1 Transcription Factor / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology; D009024:Morphogenesis / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000080462:Acyclic Monoterpenes; D018398:Homeodomain Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; D039821:Monoterpenes; D011758:Pyrroles; C105686:SU 5402; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D014212:Tretinoin; C007076:citral
keywords: Chick embryo; Craniofacial development; Fibroblast growth factor; LIM homeodomain; Lhx8; Retinoic acid