From the cover: Gene networks in development and evolution special feature Sackler colloquium: Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo

Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2009; 105(51):20089-94. DOI: 10.1073/pnas.0806442105
Source: PubMed


We dissect the transcriptional regulatory relationships coordinating the dynamic expression patterns of two signaling genes, wnt8 and delta, which are central to specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis shows that transcription of the gene encoding the Notch ligand Delta is activated by the widely expressed Runx transcription factor, but spatially restricted by HesC-mediated repression through a site in the delta 5'UTR. Spatial transcription of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus represses the repressor of delta, thereby permitting its transcription. The blimp1 gene is itself linked into a feedback circuit that includes the wnt8 signaling ligand gene, and we showed earlier that this circuit generates an expanding torus of blimp1 and wnt8 expression. The finding that delta expression is also controlled at the cis-regulatory level by the blimp1-wnt8 torus-generating subcircuit now explains the progression of Notch signaling from the mesoderm to the endoderm of the developing embryo. Thus the specific cis-regulatory linkages of the gene regulatory network encode the coordinated spatial expression of Wnt and Notch signaling as they sweep outward across the vegetal plate of the embryo.

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    • "Heterochrony in the deployment of the skeletogenic GRN is also reflected in a program of late larval skeletogenesis in euechinoids. After the larva begins to feed, several additional skeletal elements arise that are separate from the early, embryonic skeleton (Okazaki, 1975; Smith et al., 2008). These skeletal elements are secreted, at least in part, by SMCs that ingress late in gastrulation (Yajima, 2007). "
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    ABSTRACT: A central challenge of developmental and evolutionary biology is to explain how anatomy is encoded in the genome. Anatomy emerges progressively during embryonic development, as a consequence of morphogenetic processes. The specialized properties of embryonic cells and tissues that drive morphogenesis, like other specialized properties of cells, arise as a consequence of differential gene expression. Recently, gene regulatory networks (GRNs) have proven to be powerful conceptual and experimental tools for analyzing the genetic control and evolution of developmental processes. A major current goal is to link these transcriptional networks directly to morphogenetic processes. This review highlights three experimental models (sea urchin skeletogenesis, ascidian notochord morphogenesis, and the formation of somatic muscles in Drosophila) that are currently being used to analyze the genetic control of anatomy by integrating information of several important kinds: 1) morphogenetic mechanisms at the molecular, cellular and tissue levels that are responsible for shaping a specific anatomical feature, 2) the underlying GRN circuitry deployed in the relevant cells, and 3) modifications to gene regulatory circuitry that have accompanied evolutionary changes in the anatomical feature. © 2013 Wiley Periodicals, Inc.
    genesis 06/2013; 51(6). DOI:10.1002/dvg.22380 · 2.02 Impact Factor
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    • "Finally, though this refers to all the NSM, more recent results show that the control of hesC expression needs further examination. hesC clearance from the NSM is what allows delta to be expressed there after about 19 hpf (Sweet et al., 2002; Revilla-i-Domingo et al., 2007; Smith and Davidson, 2008). As we see in Figs. 1 and 5, this is the only regulatory gene within the NSM that does not respect the oral/ aboral regulatory state segregation. "
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    ABSTRACT: Specification of the non-skeletogenic mesoderm (NSM) in sea urchin embryos depends on Delta signaling. Signal reception leads to expression of regulatory genes that later contribute to the aboral NSM regulatory state. In oral NSM, this is replaced by a distinct oral regulatory state in consequence of Nodal signaling. Through regulome wide analysis we identify the homeobox gene not as an immediate Nodal target. not expression in NSM causes extinction of the aboral regulatory state in the oral NSM, and expression of a new suite of regulatory genes. All NSM specific regulatory genes are henceforth expressed exclusively, in oral or aboral domains, presaging the mesodermal cell types that will emerge. We have analyzed the regulatory linkages within the aboral NSM gene regulatory network. A linchpin of this network is gataE which as we show is a direct Gcm target and part of a feedback loop locking down the aboral regulatory state.
    Developmental Biology 12/2012; 375(1). DOI:10.1016/j.ydbio.2012.11.033 · 3.55 Impact Factor
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    • "In summary, cis-regulatory evidence surrounding the SM double negative gate now extends from the pmar1 and hesC genes (Smith and Davidson, 2008) to the tbr (Wahl et al, 2009), delta (Revilla et al, 2007; Smith et al, 2008), and alx1 genes immediately downstream, and as a result of this study both the spatial and temporal particularities of alx1 expression have now been incorporated in a consistent explanatory framework based ultimately in genomic regulatory sequence design. "
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    ABSTRACT: Deployment of the gene-regulatory network (GRN) responsible for skeletogenesis in the embryo of the sea urchin Strongylocentrotus purpuratus is restricted to the large micromere lineage by a double negative regulatory gate. The gate consists of a GRN subcircuit composed of the pmar1 and hesC genes, which encode repressors and are wired in tandem, plus a set of target regulatory genes under hesC control. The skeletogenic cell state is specified initially by micromere-specific expression of these regulatory genes, viz. alx1, ets1, tbrain and tel, plus the gene encoding the Notch ligand Delta. Here we use a recently developed high throughput methodology for experimental cis-regulatory analysis to elucidate the genomic regulatory system controlling alx1 expression in time and embryonic space. The results entirely confirm the double negative gate control system at the cis-regulatory level, including definition of the functional HesC target sites, and add the crucial new information that the drivers of alx1 expression are initially Ets1, and then Alx1 itself plus Ets1. Cis-regulatory analysis demonstrates that these inputs quantitatively account for the magnitude of alx1 expression. Furthermore, the Alx1 gene product not only performs an auto-regulatory role, promoting a fast rise in alx1 expression, but also, when at high levels, it behaves as an auto-repressor. A synthetic experiment indicates that this behavior is probably due to dimerization. In summary, the results we report provide the sequence level basis for control of alx1 spatial expression by the double negative gate GRN architecture, and explain the rising, then falling temporal expression profile of the alx1 gene in terms of its auto-regulatory genetic wiring.
    Developmental Biology 06/2011; 357(2):505-17. DOI:10.1016/j.ydbio.2011.06.016 · 3.55 Impact Factor
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