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T Marty

Publications and source records attributed to T Marty.

9 recordsLinked to original sources
PubMed2001

Nuclear interpretation of Dpp signaling in Drosophila.

Signaling by Decapentaplegic (Dpp), a member of the TGFbeta superfamily of signaling molecules similar to vertebrate BMP2 and BMP4, has been implicated in many developmental processes in Drosophila melanogaster. Notably, Dpp acts as a long-range morphogen during imaginal disc growth and patterning. Genetic approaches led to the identification of a number of gene products that constitute the core signaling pathway. In addition to the ligand-activated heteromeric receptor complex and the signal-transducing intracellular Smad proteins, Dpp signaling requires two nuclear proteins, Schnurri (Shn) and Brinker (Brk), to prime cells for Dpp responsiveness. A complex interplay between the nuclear factors involved in Dpp signaling appears to control the transcriptional readout of the Dpp morphogen gradient. It remains to be seen whether similar molecular mechanisms operate in the nucleus in vertebrate systems.

Animals↗
PubMed2001

A HOX complex, a repressor element and a 50 bp sequence confer regional specificity to a DPP-responsive enhancer.

A central theme during development and homeostasis is the generation of cell type-specific responses to the action of a limited number of extant signaling cascades triggered by extracellular ligands. The molecular mechanisms by which information from such signals are integrated in responding cells in a cell-type specific manner remain poorly understood. We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these two elements can reproduce the expression of lab550, either with regard to expression level or with regard to spatial restriction. The isolated DPPRE of lab550 responds extremely weakly to DPP. Interestingly, we found that the inducibility of this DPPRE is weak because it is tuned down by the action of a repressor element. This repressor element and an additional 50 bp element appear to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly link the DPP response to the homeotic input. The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex.

Animals↗
PubMed2000

Schnurri mediates Dpp-dependent repression of brinker transcription.

Signalling by Decapentaplegic (Dpp), a member of the TGFbeta superfamily of signalling molecules, controls many aspects of Drosophila development by activating and repressing target genes. Several essential components of the Dpp signalling pathway have been identified, including the Dpp receptors Punt and Thick veins (Tkv) as well as the cytoplasmic mediators Mad and Medea. For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene. Here we 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.

Animals↗
PubMed1999

Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.

To regulate their target genes, the Hox proteins of Drosophila often bind to DNA as heterodimers with the homeodomain protein Extradenticle (EXD). For EXD to bind DNA, it must be in the nucleus, and its nuclear localization requires a third homeodomain protein, Homothorax (HTH). Here we show that a conserved N-terminal domain of HTH directly binds to EXD in vitro, and is sufficient to induce the nuclear localization of EXD in vivo. However, mutating a key DNA binding residue in the HTH homeodomain abolishes many of its in vivo functions. HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer. Using a dominant negative form of HTH we provide evidence that similar complexes are important for several Hox- and exd-mediated functions in vivo. These data suggest that Hox proteins often function as part of a multiprotein complex, composed of HTH, Hox, and EXD proteins, bound to DNA.

Amino Acid Sequence↗
PubMed1997

Synergistic activation of a Drosophila enhancer by HOM/EXD and DPP signaling.

The homeotic proteins encoded by the genes of the Drosophila HOM and the vertebrate HOX complexes do not bind divergent DNA sequences with a high selectivity. In vitro, HOM (HOX) specificity can be increased by the formation of heterodimers with Extradenticle (EXD) or PBX homeodomain proteins. We have identified a single essential Labial (LAB)/EXD-binding site in a Decapentaplegic (DPP)-responsive enhancer of the homeotic gene lab which drives expression in the developing midgut. We show that LAB and EXD bind cooperatively to the site in vitro, and that the expression of the enhancer in vivo requires exd and lab function. In addition, point mutations in either the EXD or the LAB subsite compromise enhancer function, strongly suggesting that EXD and LAB bind to this site in vivo. Interestingly, we found that the activity of the enhancer is only stimulated by DPP signaling significantly upon binding of LAB and EXD. Thus, the enhancer appears to integrate positional information via the homeotic gene lab, and spatiotemporal information via DPP signaling; only when these inputs act in concert in an endodermal cell is the enhancer fully active. Our results illustrate how a tissue-specific response to DPP can be generated through synergistic effects on an enhancer carrying both DPP- and HOX-responsive sequences.

Animals↗
PubMed1996

[Self-expanding endoluminal vascular prosthesis: experimental basis and in-vivo evaluation].

The present study investigates the physical properties and the in vivo application of in vivo of a self-expandable stent (Wallstent) with an incorporated sealant of microporous polyurethane. Measurements of diameter and length as a function axial load featured the data for the calculation for radial pressure. Porosity control was assessed in comparison to non gelatin-sealed knitted Dacron. 11 stents on a 11.5F catheter were inserted in the aorta of three minipigs and evaluated by pressure measurement and angiography. The coverage of the stent causes an increase of 0.05-0.1 bar of radial pressure. The graph received by calculations demonstrates the corresponding pressure for every given diameter of the stents. Porosity is similar to the Dacron graft. The patency-rate is 100%. Characteristics of this covered stents meet requirements of an endovascular prostheses. Exclusion of fistulas and small aneurysms seems to be possible.

Animals↗
PubMed1995

An absolute requirement for both the type II and type I receptors, punt and thick veins, for dpp signaling in vivo.

TGF beta elicits diverse cellular responses by signaling through receptor complexes formed by two distantly related transmembrane serine/threonine kinases called type II and type I receptors. Previous studies have indicated that the product of the Drosophila thick veins (tkv) gene is a type I receptor for decapentaplegic (dpp). Here, we show that the Drosophila gene punt encodes a homolog of a vertebrate type II receptor, and we demonstrate that punt, like tkv, is essential in vivo for dpp-dependent patterning processes. Because no dpp-related signalling is apparent in the absence of either the punt or tkv receptor, we infer that both receptors act in concert to transduce the dpp signal and that their functions cannot be replaced by the other extant type II and I receptors.

Activin Receptors↗
PubMed1995

Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc.

During animal development, cell proliferation is controlled in many cases by regulation of the G1 to S phase transition. Studies of mammalian tissue culture cells have shown that the G1-specific cyclin, cyclin E, can be rate limiting for progression from G1 to S phase. During Drosophila development, down-regulation of cyclin E is required for G1 arrest in terminally differentiating embryonic epidermal cells. Whether cyclin E expression limits progression into S phase in proliferating, as opposed to differentiating, cells during development has not been investigated. Here we show that Drosophila cyclin E (DmcycE) protein is absent in G1 phase cells but appears at the onset of S phase in proliferating cells of the larval optic lobe and eye imaginal disc. We have examined cells in the eye imaginal epithelium, where a clearly defined developmentally regulated G1 to S phase transition occurs. Ectopic expression of DmcycE induces premature entry of most of these G1 cells into S phase. Thus in these cells, control of DmcycE expression is required for regulated entry into S phase. Significantly, a band of eye imaginal disc cells in G1 phase was not induced to enter S phase by ectopic expression of DmcycE. This provides evidence for additional regulatory mechanisms that operate during G1 phase to limit cell proliferation during development. These results demonstrate that the role of cyclin E in regulating progression into S phase in mammalian tissue culture cells applies to some, but not all, cells during Drosophila development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗