title: REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development.
abstract: The transcriptional regulator RERE/Atrophin-2 (RERE) is required for the normal patterning of the early vertebrate embryo, including the central nervous system, pharyngeal arches, and limbs. Consistent with a role as a transcriptional corepressor, RERE binds histone deacetylase 1 and 2 (HDAC1/2), and orphan nuclear receptors such as Tlx. Here, we identify the zebrafish babyface (bab) as a mutant in rerea and show that it interacts genetically with fibroblast growth factor 8 (fgf8). We suggest that this finding is largely due to its interactions with HDAC, because genetic or pharmacological disruptions of HDAC phenocopy many features of the bab mutant. Furthermore, removing the functions of either REREa or HDAC synergizes with loss of Fgf8 function to disrupt posterior mesoderm formation during somitogenesis, midbrain-hindbrain boundary maintenance, and pharyngeal cartilage development. Together, these results reveal novel in vivo roles for REREa in HDAC-mediated regulation of Fgf signaling. We present a model for RERE-dependent patterning in which tissue-specific transcriptional repression, by means of an REREa-HDAC complex, modulates growth factor signaling during embryogenesis.
authors.affiliation: Max-Planck Institute of Immunobiology, Freiburg, Germany. nplaster@uci.edu
authors.forename: Nikki
authors.initials: N
authors.lastname: Plaster
authors.forename: Carmen
authors.initials: C
authors.lastname: Sonntag
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schilling
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammerschmidt
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006655:Histone Deacetylases / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D029961:Zebrafish Proteins; C517774:fgf8a protein, zebrafish; C513129:rerea protein, zebrafish; D005346:Fibroblast Growth Factors; D006655:Histone Deacetylases