Publications by authors named "Gerd-Joerg Rauch"

2 Publications

  • Page 1 of 1

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

Genes Dev 2004 Jul 15;18(13):1565-76. Epub 2004 Jun 15.

Center for Developmental Genetics, School of Medicine and Biomedical Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.

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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http://dx.doi.org/10.1101/gad.296004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC443519PMC
July 2004

lockjaw encodes a zebrafish tfap2a required for early neural crest development.

Development 2003 Dec 8;130(23):5755-68. Epub 2003 Oct 8.

Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.

The neural crest is a uniquely vertebrate cell type that gives rise to much of the craniofacial skeleton, pigment cells and peripheral nervous system, yet its specification and diversification during embryogenesis are poorly understood. Zebrafish homozygous for the lockjaw (low) mutation show defects in all of these derivatives and we show that low (allelic with montblanc) encodes a zebrafish tfap2a, one of a small family of transcription factors implicated in epidermal and neural crest development. A point mutation in low truncates the DNA binding and dimerization domains of tfap2a, causing a loss of function. Consistent with this, injection of antisense morpholino oligonucleotides directed against splice sites in tfap2a into wild-type embryos produces a phenotype identical to low. Analysis of early ectodermal markers revealed that neural crest specification and migration are disrupted in low mutant embryos. TUNEL labeling of dying cells in mutants revealed a transient period of apoptosis in crest cells prior to and during their migration. In the cranial neural crest, gene expression in the mandibular arch is unaffected in low mutants, in contrast to the hyoid arch, which shows severe reductions in dlx2 and hoxa2 expression. Mosaic analysis, using cell transplantation, demonstrated that neural crest defects in low are cell autonomous and secondarily cause disruptions in surrounding mesoderm. These studies demonstrate that low is required for early steps in neural crest development and suggest that tfap2a is essential for the survival of a subset of neural crest derivatives.
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http://dx.doi.org/10.1242/dev.00575DOI Listing
December 2003