Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development
- 1 October 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in Genetics
- Vol. 174 (2), 735-752
- https://doi.org/10.1534/genetics.106.061523
Abstract
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 microarray-based 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.Keywords
This publication has 78 references indexed in Scilit:
- Expression of a heparan sulfate remodeling enzyme, heparan sulfate 6-O-endosulfatase sulfatase FP2, in the rat nervous systemDevelopmental Brain Research, 2005
- Transcriptome Analysis of Zebrafish Embryogenesis Using MicroarraysPLoS Genetics, 2005
- Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneuronesDevelopment, 2005
- The you Gene Encodes an EGF-CUB Protein Essential for Hedgehog Signaling in ZebrafishPLoS Biology, 2005
- WebLogo: A Sequence Logo Generator: Figure 1Genome Research, 2004
- Tbx1is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancerGenes & Development, 2003
- Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specificationGenes & Development, 2002
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001
- Patterning activities of vertebrate hedgehog proteins in the developing eye and brainCurrent Biology, 1995
- Stages of embryonic development of the zebrafishDevelopmental Dynamics, 1995