title: Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis.
abstract: Apoptosis is an important mechanism for sculpting morphology. However, the molecular cascades that control apoptosis in developing limb buds remain largely unclear. Here, we show that MafB was specifically expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosis, whereas MafB/cJun heterodimers promoted apoptosis for sculpting the shape of the limbs. Chromatin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulatory elements controlled by Maf and Jun. Functional analyses revealed that expression of p63 and p73, key components known to arrest the cell cycle, was directly activated by MafB and cJun. Our data suggest that dimeric combinations of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and that MafB/cJun heterodimers lead to apoptosis via activation of p63 and p73.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-17, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Natsuno
authors.initials: N
authors.lastname: Suda
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-34, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nakato
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-17, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shirakawa
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Masashige
authors.initials: M
authors.lastname: Bando
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katou
authors.affiliation: Graduate School of Medical Life Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down Road, Bath BA2 7AY, UK.
authors.forename: Cheryll
authors.initials: C
authors.lastname: Tickle
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-17, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan mitanaka@bio.titech.ac.jp.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002470:Cell Survival; D002642:Chick Embryo; D002645:Chickens; D015536:Down-Regulation / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018878:Limb Buds / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics; D011485:Protein Binding; D055503:Protein Multimerization; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D051258:MafB Transcription Factor; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014212:Tretinoin
keywords: AP-1 transcription factor; Chick; Limb