title: Distinct effects of Hoxa2 overexpression in cranial neural crest populations reveal that the mammalian hyomandibular-ceratohyal boundary maps within the styloid process.
abstract: Most gnathostomata craniofacial structures derive from pharyngeal arches (PAs), which are colonized by cranial neural crest cells (CNCCs). The anteroposterior and dorsoventral identities of CNCCs are defined by the combinatorial expression of Hox and Dlx genes. The mechanisms associating characteristic Hox/Dlx expression patterns with the topology and morphology of PAs derivatives are only partially known; a better knowledge of these processes might lead to new concepts on the origin of taxon-specific craniofacial morphologies and of certain craniofacial malformations. Here we show that ectopic expression of Hoxa2 in Hox-negative CNCCs results in distinct phenotypes in different CNCC subpopulations. Namely, while ectopic Hoxa2 expression is sufficient for the morphological and molecular transformation of the first PA (PA1) CNCC derivatives into the second PA (PA2)-like structures, this same genetic alteration does not provoke the transformation of derivatives of other CNCC subpopulations, but severely impairs their development. Ectopic Hoxa2 expression results in the transformation of the proximal Meckel's cartilage and of the malleus, two ventral PA1 CNCCs derivatives, into a supernumerary styloid process (SP), a PA2-derived mammalian-specific skeletal structure. These results, together with experiments to inactivate and ectopically activate the Edn1-Dlx5/6 pathway, indicate a dorsoventral PA2 (hyomandibular/ceratohyal) boundary passing through the middle of the SP. The present findings suggest context-dependent function of Hoxa2 in CNCC regional specification and morphogenesis, and provide novel insights into the evolution of taxa-specific patterning of PA-derived structures.
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kitazawa
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Fujisawa
authors.affiliation: Evolution des Régulations Endocriniennes, CNRS, UMR7221, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75231 Paris Cedex 05, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Narboux-Nême
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Laboratory for Systems Biology and Medicine, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan; Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Laboratory for Systems Biology and Medicine, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Laboratory for Systems Biology and Medicine, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan; Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.affiliation: Division of Genome Science, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Laboratory for Systems Biology and Medicine, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ki-Sung
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Uchijima
authors.affiliation: Division of Cardiovascular Development and Differentiation, Medical Research Institute, Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Division of Cardiovascular Development and Differentiation, Medical Research Institute, Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyagawa-Tomita
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; Faculté de chirurgie dentaire, 1, place de l'hôpital, 67 000 Strasbourg, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Minoux
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.affiliation: Evolution des Régulations Endocriniennes, CNRS, UMR7221, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75231 Paris Cedex 05, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Levi
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan; Institute for Biology and Mathematics of Dynamical Cell Processes (iBMath), The University of Tokyo, 3-8-1 Komaba, Tokyo 153-8914, Japan. Electronic address: kuri-tky@umin.net.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000423:Alcian Blue; D000818:Animals; D000880:Anthraquinones; D001934:Branchial Region / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000880:Anthraquinones; D017931:DNA Primers; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; C010078:alizarin; D000423:Alcian Blue
keywords: Craniofacial development; Dlx; Hox; Neural crest cells; Pharyngeal arches; Styloid process