PUBLICATION

REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development

Authors
Plaster, N., Sonntag, C., Schilling, T.F., and Hammerschmidt, M.
ID
ZDB-PUB-070629-17
Date
2007
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   236(7): 1891-1904 (Journal)
Registered Authors
Hammerschmidt, Matthias, Plaster, Nikki, Schilling, Tom, Sonntag, Carmen
Keywords
RERE, Atrophin-2, HDAC, Fgf8, zebrafish, craniofacial development, mesoderm formation
MeSH Terms
  • Animals
  • Down-Regulation/physiology
  • Fibroblast Growth Factors/physiology*
  • Histone Deacetylases/physiology*
  • Intracellular Signaling Peptides and Proteins/physiology*
  • Signal Transduction/physiology*
  • Zebrafish/embryology*
  • Zebrafish Proteins/physiology*
PubMed
17576618 Full text @ Dev. Dyn.
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.
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