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.[Keywords: Iguana; Gli; hedgehog signaling; zebrafish; muscle; DzipI] Supplemental material is available at http://www.genesdev.org.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes. Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map to match them with mapped candidate genes and expressed sequence tags (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions, as well as for the dog, rat and mouse. For our map of the zebrafish genome, we used an existing RH panel and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.

Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores.DOI: http://dx.doi.org/10.7554/eLife.05125.001

A polyphenism discovered to consist of five discrete morphotypes shows that extreme diversification is possible within single species.

Highlights d Phylotranscriptomics resolves the evolutionary history of Pristionchus nematodes d Hermaphroditsm arose at least six times independently within the genus d Gene loss in all hermaphroditic lineages is accelerated d Young and male-specific genes are preferentially lost