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XB-ART-256
BMC Dev Biol. September 29, 2006; 6 27.

Genomic analysis of Xenopus organizer function.

Hufton AL , Vinayagam A , Suhai S , Baker JC .


Abstract
Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. The two primary activities of the organizer, BMP and Wnt inhibition, can regulate a spectrum of genes that pattern essentially all aspects of the embryo during gastrulation. As our knowledge of organizer signaling grows, it is imperative that we begin knitting together our gene-level knowledge into genome-level signaling models. The goal of this paper was to identify complete lists of genes regulated by different aspects of organizer signaling, thereby providing a deeper understanding of the genomic mechanisms that underlie these complex and fundamental signaling events. To this end, we ectopically overexpress Noggin and Dkk-1, inhibitors of the BMP and Wnt pathways, respectively, within ventral tissues. After isolating embryonic ventral halves at early and late gastrulation, we analyze the transcriptional response to these molecules within the generated ectopic organizers using oligonucleotide microarrays. An efficient statistical analysis scheme, combined with a new Gene Ontology biological process annotation of the Xenopus genome, allows reliable and faithful clustering of molecules based upon their roles during gastrulation. From this data, we identify new organizer-related expression patterns for 19 genes. Moreover, our data sub-divides organizer genes into separate head and trunk organizing groups, which each show distinct responses to Noggin and Dkk-1 activity during gastrulation. Our data provides a genomic view of the cohorts of genes that respond to Noggin and Dkk-1 activity, allowing us to separate the role of each in organizer function. These patterns demonstrate a model where BMP inhibition plays a largely inductive role during early developmental stages, thereby initiating the suites of genes needed to pattern dorsal tissues. Meanwhile, Wnt inhibition acts later during gastrulation, and is essential for maintenance of organizer gene expression throughout gastrulation, a role which may depend on its ability to block the expression of a host of ventral, posterior, and lateral fate-specifying factors.

PubMed ID: 16756679
PMC ID: PMC1513553
Article link: BMC Dev Biol.
Grant support: R01 HD41557 NICHD NIH HHS , R01 HD041557 NICHD NIH HHS , R01 HD41557 NICHD NIH HHS

Genes referenced: aplnr arhgef3.2 crx dkk1 dlx2 foxa4 foxd4l1.1 frzb gadd45g gsc hes6.1 hes6.2 kif26a lhx1 lhx2 lmo4.2 lrig2 nog otx2 pnp rasl11b sox2 szl xarp znf703


References:
Altmann, 2001, Pubmed, Xenbase[+]


Article Images: [+] show captions

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