The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo.

Ip, Y. Tony; Park, R E; Kosman, David; Bier, Ethan; Levine, Michael

doi:10.1101/gad.6.9.1728

Cited by 313 publications

(338 citation statements)

References 51 publications

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“…TWIST1 represses E-cadherin, which results in the activation of mesenchymal markers and cell motility suggesting that TWIST1 promotes epithelial-to-mesenchymal transition. TWIST1 may also regulate the expression of the bHLH repressor SNAIL that acts as a boundary repressor by downregulating the expression of ectodermal genes within the mesoderm (Ip et al, 1992). The HIF pathway can also regulate E-Cadherin repression, presumably via SNAIL (Esteban et al, 2006).…”

Section: Twist1 Is a Target Of Hif-2a Eh Gort Et Almentioning

confidence: 99%

The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2α

et al. 2007

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Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that play a crucial role in oxygen homeostasis. Intratumoral hypoxia and genetic alterations lead to HIF activity, which is a hallmark of solid cancer and is associated with poor clinical outcome. HIF activity is regulated by an evolutionary conserved mechanism involving oxygen-dependent HIFa protein degradation. To identify novel components of the HIF pathway, we performed a genome-wide RNA interference screen in Caenorhabditis elegans, to suppress HIF-dependent phenotypes, like egg-laying defects and hypoxia survival. In addition to hif-1 (HIFa) and aha-1 (HIFb), we identified hlh-8, gska-3 and spe-8. The hlh-8 gene is homologous to the human oncogene TWIST1. We show that TWIST1 expression in human cancer cells is enhanced by hypoxia in a HIF-2a-dependent manner. Furthermore, intronic hypoxia response elements of TWIST1 are regulated by HIF-2a, but not HIF-1a. These results identify TWIST1 as a direct target gene of HIF-2a, which may provide insight into the acquired metastatic capacity of hypoxic tumors.

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Section: Twist1 Is a Target Of Hif-2a Eh Gort Et Almentioning

confidence: 99%

The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2α

et al. 2007

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“…By comparison, enhancers of type II genes, such as rhomboid (Fig. 1C), contain highaffinity Dl-binding sites that are bound and activated by the lower levels of Dl that are present in the ventral neuroectoderm (Ip et al, 1992a). Recent computational analysis of a large set of Dl-responsive enhancers from the genomes of D. melanogaster and related species has confirmed that Dl affinity is a major determinant of the expression domains of Dl target genes (Papatsenko and Levine, 2005).…”

Section: Binding-site Affinitymentioning

confidence: 99%

The interpretation of morphogen gradients

Ashe

Briscoe²

2006

Development

452

381

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DEVELOPMENT 385Morphogens act as graded positional cues that control cell fate specification in many developing tissues. This concept, in which a signalling gradient regulates differential gene expression in a concentration-dependent manner, provides a basis for understanding many patterning processes. It also raises several mechanistic issues, such as how responding cells perceive and interpret the concentration-dependent information provided by a morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Here, we review recent work on the molecular features of morphogen signalling that facilitate the interpretation of graded signals and attempt to identify some emerging common principles. IntroductionThe transformation of the spatial distribution of naïve cells in a developing tissue into an organised arrangement of cell differentiation is fundamental to the development of multicellular organisms. More than a century ago, evidence began to accumulate that cells receive 'positional information' that instructs them to develop in specific ways, depending on their location within a tissue (Wolpert, 1996). Over the intervening decades, the potential for signalling gradients to provide this positional information has become a much-investigated and -debated subject, and the term 'morphogen' has been coined to describe such signals. Today the morphogen concept continues to form the basis of many models of pattern formation (Lewis et al., 1977;Green and Smith, 1991;Gurdon and Bourillot, 2001;Tabata and Takei, 2004). Typically, in current models it is proposed that a signal produced from a defined localised source forms a concentration gradient as it spreads through surrounding tissue (Fig. 1A). The graded signal then acts directly on cells, in a concentration-dependent manner, to specify gene expression changes and cell fate selection. Thus, the concentration of ligand provides cells with a measure of their position relative to the source of the signal and organises the pattern of cell differentiation. Experimental evidence from tissues in both vertebrates and invertebrates indicates that several molecules appear to function as graded signals. The roles of these signals range from the establishment of the initial polarities of embryos to specification of cell identity in specific tissues, notably limb appendages and the nervous system in both vertebrates and Drosophila. The examples we focus on in this review are introduced in Fig. 1. Evidence in support of these signals acting as graded morphogens has been summarised in recent reviews (Gurdon and Bourillot, 2001;Tabata and Takei, 2004).Although the morphogen concept has provided an enduring and valid framework for understanding pattern formation, it raises many mechanistic issues. Much attention has focused on how the distribution of a morphogen through a tissue establishes and maintains a gradient of activity (Vincent and Dubois, 2002;Tabata and Takei, 2004); however, how the signal is perceived and interpreted in a grad...

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“…7). Prior to esg, rho transcription is activated within the neuroectoderm anlage by Dorsal and is repressed within the mesoderm anlage by sna and twi (Ip et al 1992). Consequently, rho transcript and protein form gradients with their highest point at the boundary between the anlagen for the mesoderm and neuroectoderm (Bier et al 1990;Sturtevant et al 1994).…”

Section: Der-dependent Repression Determines Three Dorsoventral Domaimentioning

confidence: 99%

**Role of the Drosophila EGF receptor in determination of the dorsoventral domains of escargot expression during primary neurogenesis**

Yagi¹,

Hayashi²

1997

Genes to Cells

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Background: Primary neurogenesis in the central nervous system of insects and vertebrates occurs in three dorsoventral domains in each side of the neuroectoderm. Among the three dorsoventral domains of the Drosophila neuroectoderm, the medial and lateral columns express the zinc-finger gene escargot (esg), whereas the intermediate column does not. We studied esg expression as a probe to investigate the mechanism of neuroectoderm patterning.

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The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo.

Cited by 313 publications

References 51 publications

The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2α

The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2α

The interpretation of morphogen gradients

**Role of the Drosophila EGF receptor in determination of the dorsoventral domains of escargot expression during primary neurogenesis**

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