PUBLICATION

iguana encodes a novel zinc-finger protein with coiled-coil domains essential for Hedgehog signal transduction in the zebrafish embryo

Authors
Wolff, C., Roy, S., Lewis, K.E., Schauerte, H., Joerg-Rauch, G., Kirn, A., Weiler, C., Geisler, R., Haffter, P., Ingham, P.W.
ID
ZDB-PUB-040617-7
Date
2004
Source
Genes & Development   18(13): 1565-1576 (Journal)
Registered Authors
Geisler, Robert, Haffter, Pascal, Ingham, Philip, Kirn, Anette, Lewis, Katharine E., Roy, Sudipto, Schauerte, Heike, Weiler, Christian, Wolff, Christian
Keywords
Iguana, Gli, hedgehog signaling, zebrafish, muscle, DzipI
MeSH Terms
  • Animals
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Drosophila Proteins*
  • Embryo, Nonmammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Molecular Sequence Data
  • Mutation
  • Oncogene Proteins/genetics
  • Oncogene Proteins/metabolism
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled/metabolism
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism
  • Signal Transduction*
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zinc Fingers*
PubMed
15198976 Full text @ Genes & Dev.
Abstract
Signaling by lipid-modified secreted glycoproteins of the Hedgehog family play fundamental roles during pattern formation in animal development and in humans; dysfunction of Hedgehog pathway components is frequently associated with a variety of congenital abnormalities and cancer. Transcriptional regulation of Hedgehog target genes is mediated by members of the Gli zinc-finger transcription factors. The relative nuclear concentrations of Gli activator (Gli(act)) and repressor (Gli(rep)) forms, together with their nucleocytoplasmic trafficking, appear to be critical determinants for target gene expression. Whereas such stringent controls of Gli activity are critical in ensuring appropriate levels of pathway activation, the mechanisms by which these processes are regulated remain inadequately understood. Here, using genetic analysis, we show that the zebrafish iguana gene product acts downstream of the Smoothened protein to modulate Gli activity in the somites of the developing embryo. Positional cloning reveals that iguana encodes the zebrafish ortholog of Dzip1, a novel zinc-finger/coiled-coil domain protein that we show can shuttle between the cytoplasm and nucleus in a manner correlated with Hedgehog pathway activity.
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Human Disease / Model
Sequence Targeting Reagents
Fish
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Mapping