Marty T., Muller B., Basler K. and Affolter M. (2000) Schnurri mediates Dpp-dependent repression of brinker transcription. Nat. Cell Biol. 2: 745-749.
Torres-Vazquez J., Park S., Warrior R. and Arora K. (2001) The transcription factor Schnurri plays a dual role in mediating Dpp signaling during embryogenesis. Development 128: 1657-1670.
Decapentaplegic (Dpp), a homolog of vertebrate bone morphogenic protein 2/4, is crucial for embryonic patterning and cell fate specification in Drosophila. Dpp signaling triggers nuclear accumulation of the Smads Mad and Medea. For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene. Both investigator teams show that Schnurri (Shn), a large zinc-finger protein, is essential for Dpp-mediated repression of brk transcription; in contrast, Shn is not required for target-gene activation. Thus, the Dpp signalling pathway bifurcates, downstream of the signal-mediating SMAD proteins, into a Shn-dependent pathway leading to brk repression and a Shn-independent pathway leading to gene activation. The existence of several Shn-like proteins in vertebrates and the observation that Brk functions in BMP signalling in Xenopus indicates that a similar regulatory cascade may be conserved in higher organisms.
Ashe H.L. and Levine M. (1999) Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Nature 398: 427-431
A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidermis, with peak Dpp signalling activity specifying amnioserosa. The proteins Short gastrulation (Sog) and Tolloid (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp or the related ligand Screw, and is subsequently processed by the protease Tld. Paradoxically, Sog appears to be required for amnioserosa formation, which is specified by . This study shows that ectopic expression of sog using the even-skipped stripe-2 enhancer redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo. Dpp activity is diminished near the Sog stripe while Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation. The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The heterologous Dpp inhibitor Noggin inhibits Dpp signalling but fails to augment Dpp activity. These authors suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.
Ashe H.L., Mannervik M. and Levine M. (2000) Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo. Development 127: 3305-3312
The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient of two TGFß signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut the dorsal ectoderm. This study examines the expression of a number of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp, Sog and Brk expression. Brk was found to repress two target genes, tailup and pannier, that exhibit different limits of expression within the dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression. We also present evidence that the activation of Dpp/Scw target genes depends on the Drosophila homolog of the CBP histone acetyltransferase.
Zhang H., Levine M. and Ashe H.L.(2001) Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo. Genes Dev. 15: 261-266
A Dpp activity gradient specifies multiple thresholds of gene expression in the dorsal ectoderm of the early embryo. Some of these thresholds depend on a putative repressor, Brinker, which is expressed in the neurogenic ectoderm in response to the maternal Dorsal gradient and Dpp signaling. This study shows that Brinker is a sequence-specific transcriptional repressor. It binds the consensus sequence, TGGCGc/tc/t, and interacts with the Groucho corepressor through a conserved sequence motif, FKPY. An optimal Brinker binding site is contained within an 800-bp enhancer from the tolloid gene, which has been identified as a genetic target of the Brinker repressor. A tolloid-lacZ transgene containing point mutations in this site exhibits an expanded pattern of expression, suggesting that Brinker directly represses tolloid transcription.
Calleja M., Herranz H., Estella C., Casal J., Lawrence P., Simpson P. and Morata G. (2000) Generation of medial and lateral dorsal body domains by the pannier gene of Drosophila. Development 127: 3971-3980.
The pannier (pnr) gene encodes a GATA transcription factor and acts in several developmental processes in Drosophila, including embryonic dorsal closure, specification of cardiac cells and bristle determination. This study shows that pnr is expressed in the mediodorsal parts of thoracic and abdominal segments of embryos, larvae and adult flies. Its activity confers to cells adhesion properties that make them immiscible with non-expressing cells. Thus there are two genetic domains in the dorsal region of each segment: a medial (MED) region where pnr is expressed and a lateral (LAT) region where it is not. The homeobox gene iroquois (iro) is expressed in the LAT region. These regions are not formed by separate polyclones of cells, but are defined topographically. The investigators show that ectopic pnr in the wing induces MED thoracic development, indicating that pnr specifies the identity of the MED regions. Correspondingly, when pnr is removed from clones of cells in the MED domain, they sort out and apparently adopt the LAT fate. The authors propose that (1) the subdivision into MED and LAT regions is a general feature of the Drosophila body plan and (2) pnr is the principal gene responsible for this subdivision. They argue that pnr acts like a classical selector gene but differs in that its expression is not propagated through cell divisions.
Grosshans J. and Wieschaus E. (2000) A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Cell 101: 523-531.
Rapid transitions between mitosis and morphogenesis may require special mechanisms to coordinate cell shape changes. The investigators describe a novel mitotic inhibitor that acts during Drosophila gastrulation to counteract String in those cells that invaginate to form the mesoderm (see Figs. 5.33 and 5.34 in text). They have identified two genes, frühstart+ and tribbles+, that are required for this ventral inhibition. tribbles+ encodes a kinase-related protein whose RNA, however, is also present outside of the ventral region. Effective inhibition of mitosis in the cells of the ventral furrow depends on the transcription factor Snail, which triggers the ventral cell shape changes. Tribbles directly inhibits mitosis when overexpressed in a microinjection assay. The authors propose that Frühstart and Tribbles form a link between the morphogenetic movements and mitotic control.
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