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Development is controlled by a complex series of events requiring sequential gene activation. Understanding the logic of gene networks during development is necessary for a complete understanding of how genes contribute to phenotype. Pioneering work initiated in the sea urchin and Drosophila has demonstrated that reasonable transcriptional regulatory network diagrams representing early development in multicellular animals can be generated through use of appropriate genomic, genetic, and biochemical tools. Establishment of similar regulatory network diagrams for vertebrate development is a necessary step. The amphibian Xenopus has long been used as a model for vertebrate early development and has contributed greatly to the elucidation of gene regulation. Because the best and most extensively studied transcriptional regulatory network in Xenopus is that underlying the formation and function of Spemann's organizer, we describe the current status of our understanding of this gene regulatory network and its relationship to mesodermal patterning. Seventy-four transcription factors currently known to be expressed in the mesoendoderm of Xenopus gastrula were characterized according to their modes of action, DNA binding consensus sequences, and target genes. Among them, nineteen transcription factors were characterized sufficiently in detail, allowing us to generate a gene regulatory network diagram. Additionally, we discuss recent amphibian work using a combined DNA microarray and bioinformatics approach that promises to accelerate regulatory network studies.
Fig. 1. GRNs in the Xenopus mesoderm specification. (A) Marginal region of pregastrula stage embryo. The yellow area with mesh indicates the dorsal mesoderm, and the yellow area indicates the ventral marginal zone. The colored arrows and barreled lines indicate direct activation and repression of the target gene. All suspected indirect relationships have been excluded from the diagram. Transcription factors mediating growth factor signaling are indicated in boxes. Note that, in the dorsal mesoderm, Gsc and Xbra are coexpressed. (B) Marginal region of early-late gastrula stage embryo. During this period, the mesoderm is subdivided to become the dorsal (pink area), dorsolateral (hatched area), and ventrolateral mesoderm (yellow). All necessary primary references that support the arrows (direct interaction) are listed in Table 1, under “direct target genes.†The question marks denote direct activin/nodal or Wnt target genes. However, the transcription factors responsible for the induction are unknown.
Fig. 2. Structure and function of Gsc promoter. (A) A schematic diagram representing three elements within the 492-bp Gsc promoter. UE, upstream elements. Transcription factors known to bind to each of the element are indicated. (B and C). DE and PE sequences recognized by transcription factors. Homeobox binding sequences, ATTA and TAAT, are indicated in red with arrows. The black arrows indicate the region where each transcriptional factor is currently known to bind.
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