The Zebrafish-Secreted Matrix Protein You/Scube2 Is Implicated in Long-Range Regulation of Hedgehog Signaling

Kawakami, Koichi; Nojima, Yuki; Toyoda, Atsushi; Takahoko, Mikako; Satoh, Miho; Tanaka, Hideomi; Wada, Hironori; Masai, Ichiro; Terasaki, Harumi; Sakaki, Yoshiyuki; Takeda, Hiroyuki; Okamoto, Hitoshi

doi:10.1016/j.cub.2005.07.026

Cited by 28 publications

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“…This expression is distinctly expanded ventrally in embryos that lack Hh activity (Figure 8, B, E, and H). Conversely, in line with the ventralization of the neural tube on ectopic activation of Hh signaling, we found complete absence of expression of this gene from the dorsal neural cells in embryos overexpressing dnPKA (Figure 8, C (Kawakami et al 2005). In light of this, our present analysis has uncovered an interesting negative regulation that exists between Hh activity and the expression of the scube2 gene in the dorsal neural tube.…”

Section: Resultssupporting

confidence: 81%

Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development

Srinivas

Tay

et al. 2006

Genetics

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Hedgehog proteins play critical roles in organizing the embryonic development of animals, largely through modulation of target gene expression. Little is currently known, however, about the kinds and numbers of genes whose expression is controlled, directly or indirectly, by Hedgehog activity. Using techniques to globally repress or activate Hedgehog signaling in zebrafish embryos followed by microarraybased expression profiling, we have discovered a cohort of genes whose expression responds significantly to loss or gain of Hedgehog function. We have confirmed the Hedgehog responsiveness of a representative set of these genes with whole-mount in situ hybridization as well as real time PCR. In addition, we show that the consensus Gli-binding motif is enriched within the putative regulatory elements of a sizeable proportion of genes that showed positive regulation in our assay, indicating that their expression is directly induced by Hedgehog. Finally, we provide evidence that the Hedgehog-dependent spatially restricted transcription of one such gene, nkx2.9, is indeed mediated by Gli1 through a single Gli recognition site located within an evolutionarily conserved enhancer fragment. Taken together, this study represents the first comprehensive survey of target genes regulated by the Hedgehog pathway during vertebrate development. Our data also demonstrate for the first time the functionality of the Gli-binding motif in the control of Hedgehog signaling-induced gene expression in the zebrafish embryo.

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Section: Resultssupporting

confidence: 81%

Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development

Srinivas

Tay

et al. 2006

Genetics

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“…The zebrafish mutant chameleon (con) encodes Dispatched 1 (disp1), a membrane protein that is needed for Hh secretion and processing (Nakano et al, 2004). More recently identified mutants include iguana (igu), which encodes a novel protein in the Hh pathway called dZip (Sekimizu et al, 2004;Wolff et al, 2004), and you(you), which encodes the secreted EGF repeat containing protein Scube2 that regulates long range Hh signaling (Kawakami et al, 2005;Woods and Talbot, 2005).…”

Section: Resultsmentioning

confidence: 99%

Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube

Guner

Karlstrom

2007

Gene Expression Patterns

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Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly identified zebrafish mutants affect Hh signaling. dbx1a; dbx2; hlx1; hlxb9; irx1a; irx3a; irx5; nkx2.2a; nkx2.9; nkx6.1; nkx6.2; pax3; pax6a; pax7; chameleon; detour; slow muscle omitted; you-too; cyclopamine; floorplate; motor neurons Keywords Results and DiscussionSecreted proteins of the Hedgehog (Hh) family are well known for their role in patterning the vertebrate and invertebrate embryo (Ingham and McMahon, 2001). During development, Hh functions in a concentration dependent manner to influence cell differentiation (Ericson et al., 1997a). Hh can also act as a survival factor (Miao et al., 1997) or a mitogen (Dahmane et al., 2001) to help shape the embryo. The morphogen activity of Hh has been well studied in the neural tube of chick and mouse (Ericson et al., 1995;Wijgerde et al., 2002), where Hh secreted from the notochord induces floorplate and ventral neural fates based on the concentration of Hh seen by a neural progenitor cell (Echelard et al., 1993). Cells respond to Hh through a * Corresponding author (e-mail: Karlstrom@bio.umass.edu) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers t...

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“…The muscle pioneers are early-developing, Engrailed-expressing slow muscle fibers that are located at the level of the horizontal myoseptum that divides the myotome into dorsal and ventral halves (Waterman, 1969;van Raamsdonk et al, 1978van Raamsdonk et al, , 1982Felsenfeld et al, 1991;Hatta et al, 1991). The muscle pioneers, slow muscle precursors, and horizontal myoseptum are missing in embryos in which transduction of hedgehog signaling to the somites is perturbed, and the somites in these embryos are u-shaped, rather than the chevron shape seen in wild-type embryos (Currie and Ingham, 1996;Devoto et al, 1996;van Eeden et al, 1996;Blagden et al, 1997;Schauerte et al, 1998;Karlstrom et al, 1999;Lewis et al, 1999;Barresi et al, 2000;Chen et al, 2001;Coutelle et al, 2001;Du and Dienhart, 2001;Roy et al, 2001;Baxendale et al, 2004;Hirsinger et al, 2004;Sekimizu et al, 2004;Wilbanks et al, 2004;Wolff et al, 2004;Kawakami et al, 2005a;Woods and Talbot, 2005;Feng et al, 2006;van der Meer et al, 2006).…”

Section: Segmentation and Differentiation Of The Somite Derivatives Mmentioning

confidence: 99%

The genetics and embryology of zebrafish metamerism

Holley

2007

Developmental Dynamics

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The Zebrafish-Secreted Matrix Protein You/Scube2 Is Implicated in Long-Range Regulation of Hedgehog Signaling

Abstract: In the Supplemental Data of this article, the strain described as smu b571 was actually b641. The authors regret the error.

Cited by 28 publications

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Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development

Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development

Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube

The genetics and embryology of zebrafish metamerism

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