title: The Polycomb group protein Ring1b is essential for pectoral fin development.
abstract: Polycomb group (PcG) proteins are transcriptional repressors that mediate epigenetic gene silencing by chromatin modification. PcG-mediated gene repression is implicated in development, cell differentiation, stem-cell fate maintenance and cancer. However, analysis of the roles of PcG proteins in orchestrating vertebrate developmental programs in vivo has been hampered by the early embryonic lethality of several PcG gene knockouts in mice. Here, we demonstrate that zebrafish Ring1b, the E3 ligase in Polycomb Repressive Complex 1 (PRC1), is essential for pectoral fin development. We show that differentiation of lateral plate mesoderm (LPM) cells into presumptive pectoral fin precursors is initiated normally in ring1b mutants, but fin bud outgrowth is impaired. Fgf signaling, which is essential for migration, proliferation and cell-fate maintenance during fin development, is not sufficiently activated in ring1b mutants. Exogenous application of FGF4, as well as enhanced stimulation of Fgf signaling by overactivated Wnt signaling in apc mutants, partially restores the fin developmental program. These results reveal that, in the absence of functional Ring1b, fin bud cells fail to execute the pectoral fin developmental program. Together, our results demonstrate that PcG-mediated gene regulation is essential for sustained Fgf signaling in vertebrate limb development.
authors.affiliation: Department of Molecular Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Yme U
authors.initials: YU
authors.lastname: van der Velden
authors.forename: Liqin
authors.initials: L
authors.lastname: Wang
authors.forename: Maarten
authors.initials: M
authors.lastname: van Lohuizen
authors.forename: Anna-Pavlina G
authors.initials: AP
authors.lastname: Haramis
mesh_terms: D058500:Animal Fins / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D063146:Polycomb-Group Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D063146:Polycomb-Group Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029961:Zebrafish Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D044767:Ubiquitin-Protein Ligases; C574099:rnf2 protein, zebrafish