Genomes and Genes
Gene Symbol: tld
Alias: CG6868, CT21278, Dmel\CG6868, TLD, Tld, Tolloid, dTld, tolloid, CG6868-PA, tld-PA
Species: fruit fly
- Araujo H, Negreiros E, Bier E. Integrins modulate Sog activity in the Drosophila wing. Development. 2003;130:3851-64 pubmed..We propose that integrins act by binding and possibly regulating the activity/availability of different forms of Sog during pupal development through an adhesion independent mechanism. ..
- Yu K, Kang K, Heine P, Pyati U, Srinivasan S, Biehs B, et al. Cysteine repeat domains and adjacent sequences determine distinct bone morphogenetic protein modulatory activities of the Drosophila Sog protein. Genetics. 2004;166:1323-36 pubmed..Cumulatively, our analysis suggests that CR domains interact physically with adjacent protein sequences to create forms of Sog with distinct BMP modulatory activities. ..
- Hecht P, Anderson K. Extracellular proteases and embryonic pattern formation. Trends Cell Biol. 1992;2:197-202 pubmed
- Matzkin L, Merritt T, Zhu C, Eanes W. The structure and population genetics of the breakpoints associated with the cosmopolitan chromosomal inversion In(3R)Payne in Drosophila melanogaster. Genetics. 2005;170:1143-52 pubmed publisher..The distal breakpoint breaks the tolkin (tok) gene and the proximal breakpoint breaks CG31279 and the tolloid (tld) gene. Functional copies of all three genes are found at the opposite breakpoints...
- Ashe H, Levine M. Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Nature. 1999;398:427-31 pubmed..The proteins Short gastrulation (Sog) and Tolloid (Tld) are required to shape this gradient...
- Yin Z, Frasch M. Regulation and function of tinman during dorsal mesoderm induction and heart specification in Drosophila. Dev Genet. 1998;22:187-200 pubmed..We further show that Screw, a second BMP2/4-related gene product, Tolloid, a BMP1-related protein, and the zinc finger-containing protein Schnurri, are required to allow full levels of ..
- Hasson P, Muller B, Basler K, Paroush Z. Brinker requires two corepressors for maximal and versatile repression in Dpp signalling. EMBO J. 2001;20:5725-36 pubmed..Our results show that Brk utilizes multiple means to repress its endogenous target genes, allowing repression of a multitude of complex Dpp target promoters. ..
- Christian J. BMP, Wnt and Hedgehog signals: how far can they go?. Curr Opin Cell Biol. 2000;12:244-9 pubmed..Furthermore, recent studies suggest that variations in the signaling range of these molecules may be due to tissue-specific differences in intracellular processing or tissue-restricted expression of binding proteins. ..
- Ashe H. BMP signalling: synergy and feedback create a step gradient. Curr Biol. 2005;15:R375-7 pubmed..More than a decade ago, genetic evidence predicted the existence of a Dpp gradient in the early Drosophila embryo. Two recent studies finally reveal Dpp distribution, providing further insights into the mechanism of BMP gradient formation. ..
- Lepage T, Ghiglione C, Gache C. Spatial and temporal expression pattern during sea urchin embryogenesis of a gene coding for a protease homologous to the human protein BMP-1 and to the product of the Drosophila dorsal-ventral patterning gene tolloid. Development. 1992;114:147-63 pubmed..a protease described as a factor involved in bone formation, and as the recently characterized product of the tolloid gene which is required for correct dorsal-ventral patterning of the Drosophila embryo...
- Childs S, O Connor M. Two domains of the tolloid protein contribute to its unusual genetic interaction with decapentaplegic. Dev Biol. 1994;162:209-20 pubmedThe zygotic dorsal-ventral patterning gene tolloid (tld) exhibits a complex structure consisting of an N-terminal domain with sequence similarity to the astacin family of metalloproteases and a C-terminal domain composed of two EGF-like ..
- Arora K, Nusslein Volhard C. Altered mitotic domains reveal fate map changes in Drosophila embryos mutant for zygotic dorsoventral patterning genes. Development. 1992;114:1003-24 pubmed..and shrew affect cell division only in the dorsalmost cells corresponding to the amnioserosa, while the genes tolloid, screw and decapentaplegic (dpp) affect divisions in both the prospective amnioserosa and the dorsal epidermis...
- Shimmi O, Umulis D, Othmer H, O Connor M. Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell. 2005;120:873-86 pubmed..Finally, we demonstrate mathematically that heterodimer levels can be less sensitive to changes in gene dosage than homodimers, thereby providing further selective advantage for using heterodimers as morphogens...
- Holmqvist P, Boija A, Philip P, Crona F, Stenberg P, Mannervik M. Preferential genome targeting of the CBP co-activator by Rel and Smad proteins in early Drosophila melanogaster embryos. PLoS Genet. 2012;8:e1002769 pubmed publisher..We conclude that CBP occupancy in Drosophila embryos preferentially overlaps factors controlling dorso-ventral patterning and that CBP binds silent genes without causing histone hyperacetylation. ..
- Thisse C, Thisse B. Dorsoventral development of the Drosophila embryo is controlled by a cascade of transcriptional regulators. Dev Suppl. 1992;:173-81 pubmed..In addition, in cultured cells twist has been shown to be a transcriptional activator. Thus, the first events of embryonic development along the D/V axis are controlled at the transcriptional level. ..
- Belvin M, Jin Y, Anderson K. Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes Dev. 1995;9:783-93 pubmed
- Marques G, Musacchio M, Shimell M, Wünnenberg Stapleton K, Cho K, O Connor M. Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins. Cell. 1997;91:417-26 pubmed..Among these molecules, Tolloid, a putative metalloprotease related to BMP-1, enhances DPP function, while SOG, an ortholog of the Xenopus ..
- Nguyen M, Park S, Marques G, Arora K. Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV. Cell. 1998;95:495-506 pubmed..Further, we show that the extracellular protein SOG can antagonize SCW, thus limiting its ability to augment DPP signaling in a graded manner. ..
- Rushlow C, Levine M. Role of the zerknüllt gene in dorsal-ventral pattern formation in Drosophila. Adv Genet. 1990;27:277-307 pubmed
- Nguyen T, Jamal J, Shimell M, Arora K, O Connor M. Characterization of tolloid-related-1: a BMP-1-like product that is required during larval and pupal stages of Drosophila development. Dev Biol. 1994;166:569-86 pubmedThe Drosophila tolloid (tld) gene product belongs to a family of developmentally important proteins that includes bone morphogenetic protein-1 (BMP-1)...
- Mason E, Konrad K, Webb C, Marsh J. Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. Genes Dev. 1994;8:1489-501 pubmed..We propose that dorsal midline cell fate is specified by the combination of both a TSG and a DPP signal to which the dorsal midline cells are uniquely competent to respond. ..
- Yu K, Srinivasan S, Shimmi O, Biehs B, Rashka K, Kimelman D, et al. Processing of the Drosophila Sog protein creates a novel BMP inhibitory activity. Development. 2000;127:2143-54 pubmed..in vivo processing of Sog can be duplicated in vitro by treating Sog with a combination of the metalloprotease Tolloid (Tld) plus Twisted Gastrulation (Tsg), another extracellular factor involved in Dpp signaling...
- Patthy L. Genome evolution and the evolution of exon-shuffling--a review. Gene. 1999;238:103-14 pubmed
- Cho K, Blitz I. BMPs, Smads and metalloproteases: extracellular and intracellular modes of negative regulation. Curr Opin Genet Dev. 1998;8:443-9 pubmed..Recent findings in Drosophila and vertebrates suggest that BMP signaling can be modulated extracellularly and intracellularly by the availability of BMP inhibitors and Smads, respectively. ..
- Dorfman R, Shilo B. Biphasic activation of the BMP pathway patterns the Drosophila embryonic dorsal region. Development. 2001;128:965-72 pubmed..of pMad requires the ligand Screw (Scw), the Short gastrulation (Sog) protein, and cleavage of their complex by Tolloid (Tld). When the inhibitory activity of Sog is removed, Mad phosphorylation is expanded...
- Jones C, Smith J. Inductive signals. Revolving vertebrates. Curr Biol. 1995;5:574-6 pubmed..An old idea about the relationship between arthropod and vertebrate body plans has been given new life by studies of the signalling genes controlling dorsal and ventral development in Drosophila and Xenopus. ..
- Umulis D, Serpe M, O Connor M, Othmer H. Robust, bistable patterning of the dorsal surface of the Drosophila embryo. Proc Natl Acad Sci U S A. 2006;103:11613-8 pubmed..bone morphogenetic proteins (BMPs), their receptors, the BMP-binding proteins Sog and Tsg, the metalloprotease Tld, and a putative, positively regulated component that locally enhances surface binding of BMPs within the region of ..
- Mrinal N, Tomar A, Nagaraju J. Role of sequence encoded ?B DNA geometry in gene regulation by Dorsal. Nucleic Acids Res. 2011;39:9574-91 pubmed publisher..Further, we identified and characterized putative repressor motifs in Dl-target genes, which can potentially aid in functional annotation of Dorsal gene regulatory network. ..
- Saunders R, Avides M, Howard T, Gonzalez C, Glover D. The Drosophila gene abnormal spindle encodes a novel microtubule-associated protein that associates with the polar regions of the mitotic spindle. J Cell Biol. 1997;137:881-90 pubmed..required for normal spindle structure and function in Drosophila melanogaster, lies immediately adjacent the gene tolloid at 96A/B. It encodes a 220-kD polypeptide with a predicted pI of 10.8...
- Serpe M, Umulis D, Ralston A, Chen J, Olson D, Avanesov A, et al. The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila. Dev Cell. 2008;14:940-53 pubmed publisher..We also find that Cv-2 expression is controlled by BMP signaling, and these combined properties enable Cv-2 to exquisitely tune BMP signaling. ..
- Bier E. Anti-neural-inhibition: a conserved mechanism for neural induction. Cell. 1997;89:681-4 pubmed
- Yip M, Lamka M, Lipshitz H. Control of germ-band retraction in Drosophila by the zinc-finger protein HINDSIGHT. Development. 1997;124:2129-41 pubmed..Second, hindsight might function both to maintain the amnioserosa and to regulate chemical signaling from the amnioserosa to the epidermal ectoderm, thus coordinating the cell shape changes and movements that drive germ-band retraction...
- Ip Y. Transcriptional regulation. Converting an activator into a repressor. Curr Biol. 1995;5:1-3 pubmed..Dorsoventral patterning in Drosophila requires the Dorsal morphogen to act as both an activator and a repressor of transcription: an HMG1-like protein may serve to switch Dorsal from one to the other. ..
- Courey A, Huang J. The establishment and interpretation of transcription factor gradients in the Drosophila embryo. Biochim Biophys Acta. 1995;1261:1-18 pubmed
- Nakayama T, Cui Y, Christian J. Regulation of BMP/Dpp signaling during embryonic development. Cell Mol Life Sci. 2000;57:943-56 pubmed..Recent studies have shown that the BMP signal transduction cascade can be modulated at every step of this process. ..
- Rusch J, Levine M. Regulation of a dpp target gene in the Drosophila embryo. Development. 1997;124:303-11 pubmed..These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa. ..
- Arora K, Dai H, Kazuko S, Jamal J, O Connor M, Letsou A, et al. The Drosophila schnurri gene acts in the Dpp/TGF beta signaling pathway and encodes a transcription factor homologous to the human MBP family. Cell. 1995;81:781-90 pubmed..Genetic interactions and the strikingly similar phenotypes of mutations in shn and the dpp receptors encoded by thick veins and punt suggest that shn plays a downstream role in dpp signaling. ..
- Wall N, Hogan B. TGF-beta related genes in development. Curr Opin Genet Dev. 1994;4:517-22 pubmed
- Ray R, Wharton K. Twisted perspective: new insights into extracellular modulation of BMP signaling during development. Cell. 2001;104:801-4 pubmed
- Shenk M, Steele R. A molecular snapshot of the metazoan 'Eve'. Trends Biochem Sci. 1993;18:459-63 pubmed..We use the distributions of classes of transcription factors, signal transduction systems and other molecular innovations among metazoan phyla to infer some of the characteristics of the first animals. ..
- Mason E, Williams S, Grotendorst G, Marsh J. Combinatorial signaling by Twisted Gastrulation and Decapentaplegic. Mech Dev. 1997;64:61-75 pubmed..The interaction between TSG and DPP defines a novel type of combinatorial synergism. ..
- Ashe H. BMP signalling: visualisation of the Sog protein gradient. Curr Biol. 2002;12:R273-5 pubmed..Direct visualisation in the Drosophila embryo of Sog, a Dpp/Scw inhibitor, has now revealed a graded distribution established by degradation and endocytosis. ..
- Kirov N, Childs S, O Connor M, Rushlow C. The Drosophila dorsal morphogen represses the tolloid gene by interacting with a silencer element. Mol Cell Biol. 1994;14:713-22 pubmed..Here we analyze the interaction of DL with another one of its repressed targets, the tolloid (tld) gene...
- Jacobs H, Knoblich J, Lehner C. Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B. Genes Dev. 1998;12:3741-51 pubmed..However, both are required for female fertility and Cyclin B also for male fertility. ..
- Bier E. Developmental biology. A unity of opposites. Nature. 1999;398:375-6 pubmed
- Podos S, Ferguson E. Morphogen gradients: new insights from DPP. Trends Genet. 1999;15:396-402 pubmed..These reports identity additional genes and genetic circuitry necessary for this patterning system, and they highlight variations that might reflect developmental constraints within individual target cell fields. ..
- Padgett R, Das P, Krishna S. TGF-beta signaling, Smads, and tumor suppressors. Bioessays. 1998;20:382-90 pubmed..Thus, genetic and biochemical studies suggest a very simple signaling pathway, in which Smads are the primary downstream participant. ..
- Sanchez -, van Helden J -, Thieffry -. Establishement of the dorso-ventral pattern during embryonic development of drosophila melanogasater: a logical analysis. J Theor Biol. 1997;189:377-89 pubmed..Furthermore, it is predicted that if the gene snail shows autoregulation, this will not be crucial for the determination of the embryonic D-V pattern. Copyright 1997 Academic Press Limited Copyright 1997 Academic Press Limited ..
- Biehs B, Francois V, Bier E. The Drosophila short gastrulation gene prevents Dpp from autoactivating and suppressing neurogenesis in the neuroectoderm. Genes Dev. 1996;10:2922-34 pubmed
- Rusch J, Levine M. Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo. Curr Opin Genet Dev. 1996;6:416-23 pubmed
- Chang C, Hemmati Brivanlou A. Cell fate determination in embryonic ectoderm. J Neurobiol. 1998;36:128-51 pubmed..Emphasis is placed on, but not limited to, discoveries made in Xenopus, as most of our progress in understanding the ectodermal patterning is obtained from studies using this organism. ..
- Umulis D, Shimmi O, O Connor M, Othmer H. Organism-scale modeling of early Drosophila patterning via bone morphogenetic proteins. Dev Cell. 2010;18:260-74 pubmed publisher..Our results demonstrate that using bioimages to build and optimize a three-dimensional model provides significant insights into mechanisms that guide tissue patterning. ..
- Campos Ortega J. The genetics of the Drosophila achaete-scute gene complex: a historical appraisal. Int J Dev Biol. 1998;42:291-7 pubmed..Due to their intricate organization, these genes have occupied geneticists and developmental biologists for many years. Here, genetic studies on the complex are discussed from a historical point of view. ..
- Jazwinska A, Rushlow C, Roth S. The role of brinker in mediating the graded response to Dpp in early Drosophila embryos. Development. 1999;126:3323-34 pubmed..Low-level target genes, like dpp itself, tolloid and early zerknüllt, show strong ectopic expression in ventrolateral regions of brk mutant embryos; intermediate-..
- Ross J, Shimmi O, Vilmos P, Petryk A, Kim H, Gaudenz K, et al. Twisted gastrulation is a conserved extracellular BMP antagonist. Nature. 2001;410:479-83 pubmed..We show that Tsgs from different species are functionally equivalent, and conclude that Tsg is a conserved protein that functions with SOG/chordin to antagonize BMP signalling. ..
- Adamson A, Shearn A. Molecular genetic analysis of Drosophila ash2, a member of the trithorax group required for imaginal disc pattern formation. Genetics. 1996;144:621-33 pubmed..The ash2 gene is located in cytogenetic region 96A17-19 flanked by slowpoke and tolloid and is included in a cosmid that contains part of slowpoke. The ash2 transcript is 2...
- Weinmaster G. Reprolysins and astacins...alive, alive-o. Science. 1998;279:336-7 pubmed
- Fritsch C, Lanfear R, Ray R. Rapid evolution of a novel signalling mechanism by concerted duplication and divergence of a BMP ligand and its extracellular modulators. Dev Genes Evol. 2010;220:235-50 pubmed publisher..Our results demonstrate the plasticity of the BMP pathway not only in evolving new family members and new functions but also new signalling modes by redeploying key regulators in the pathway. ..
- Serpe M, Ralston A, Blair S, O Connor M. Matching catalytic activity to developmental function: tolloid-related processes Sog in order to help specify the posterior crossvein in the Drosophila wing. Development. 2005;132:2645-56 pubmedThe Drosophila tolloid (tld) and tolloid related (tlr) gene products belong to a family of developmentally important proteases that includes Bone Morphogenetic Protein 1 (Bmp1)...
- Ranz J, Caceres M, Ruiz A. Comparative mapping of cosmids and gene clones from a 1.6 Mb chromosomal region of Drosophila melanogaster in three species of the distantly related subgenus Drosophila. Chromosoma. 1999;108:32-43 pubmed..Finally, our data indicate significant statistical differences in the evolution rate of Muller's element E among lineages, a result that agrees well with the previous cytogenetic data. ..
- Raftery L, Sutherland D. Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos. Trends Genet. 2003;19:701-8 pubmed..The transition between two gradients of different shape yields new insights into the progression of Drosophila dorsal-ventral patterning and raises new issues about the mechanisms of gradient formation. ..
- Francois V, Solloway M, O Neill J, Emery J, Bier E. Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene. Genes Dev. 1994;8:2602-16 pubmed..These putative soluble Sog peptides may then diffuse into the dorsal region to antagonize the activity of Dpp, leading to the subdivision of the dorsal territory into amnioserosa and dorsal ectoderm. ..
- Dale L. Pattern formation: a new twist to BMP signalling. Curr Biol. 2000;10:R671-3 pubmed..Twisted Gastrulation has now been added to the list of proteins that regulate the activity of these molecules, providing new insights into how BMPs are made available to their signalling receptors. ..
- Upadhyai P, Campbell G. Brinker possesses multiple mechanisms for repression because its primary co-repressor, Groucho, may be unavailable in some cell types. Development. 2013;140:4256-65 pubmed publisher..Gro insufficiency during oogenesis can be explained by its downregulation in Brk-expressing cells through phosphorylation downstream of EGFR signaling. ..
- Tao Y, Zeng Z, Li J, Hartl D, Laurie C. Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. II. Mapping hybrid male sterility loci on the third chromosome. Genetics. 2003;164:1399-418 pubmed..These results are consistent with the gradual evolution of hybrid incompatibilities as a by-product of genetic divergence in allopatric populations...
- Tao Y, Chen S, Hartl D, Laurie C. Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. I. Differential accumulation of hybrid male sterility effects on the X and autosomes. Genetics. 2003;164:1383-97 pubmed..Possible mechanisms of a "large X" effect include selective fixation of new mutations that are recessive or partially recessive and the evolution of sex-ratio distortion systems...
- Riede I. Three mutant genes cooperatively induce brain tumor formation in Drosophila malignant brain tumor. Cancer Genet Cytogenet. 1996;90:135-41 pubmed..Whereas spz and tld belong to the genes inducing differentiation patterns in the embryo, yeti induces cell overgrowth...
- PELUSO C, Umulis D, Kim Y, O Connor M, Serpe M. Shaping BMP morphogen gradients through enzyme-substrate interactions. Dev Cell. 2011;21:375-83 pubmed publisher..For example, Tolloid (Tld)-like metalloproteases cleave vertebrate BMP-binding proteins called Chordins constitutively, while the ..
- Capdevila J, lzpisúa Belmonte J. Extracellular modulation of the Hedgehog, Wnt and TGF-beta signalling pathways during embryonic development. Curr Opin Genet Dev. 1999;9:427-33 pubmed
- Ferguson E, Anderson K. Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. Development. 1992;114:583-97 pubmed..1, 868-879). Here we describe the phenotypes caused by alleles of another of this set of genes, tolloid, and show that tolloid is required for dorsal, but not dorsolateral, pattern...
- O Connor M, Umulis D, Othmer H, Blair S. Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development. 2006;133:183-93 pubmed..Because these signaling pathway components are all conserved, these observations should shed light on how BMP signaling is modulated in vertebrate development. ..
- Jiang H, Hou Q, Gong Z, Liu L. Proteomic and transcriptomic analysis of visual long-term memory in Drosophila melanogaster. Protein Cell. 2011;2:215-22 pubmed publisher..These results provide insight into the molecular components influencing visual long-term memory and facilitate further studies on the roles of identified genes in memory formation. ..
- Casci T. Patterning back to front. Nat Rev Genet. 2001;2:161 pubmed
- Nicholls R, Gelbart W. Identification of chromosomal regions involved in decapentaplegic function in Drosophila. Genetics. 1998;149:203-15 pubmed..As neither of these regions has been previously implicated in dpp function, we propose that each of the deficiencies removes a novel factor or factors required for dpp function. ..
- Staehling Hampton K, Jackson P, Clark M, Brand A, Hoffmann F. Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A. Cell Growth Differ. 1994;5:585-93 pubmed
- Canty E, Garrigue Antar L, Kadler K. A complete domain structure of Drosophila tolloid is required for cleavage of short gastrulation. J Biol Chem. 2006;281:13258-67 pubmedDrosophila tolloid (TLD) is a member of a family of proteinases that play important roles in development and includes mammalian tolloid (mTLD) and bone morphogenetic protein (BMP)-1...
- Winstanley J, Sawala A, Baldock C, Ashe H. Synthetic enzyme-substrate tethering obviates the Tolloid-ECM interaction during Drosophila BMP gradient formation. elife. 2015;4: pubmed publisherMembers of the Tolloid family of metalloproteinases liberate BMPs from inhibitory complexes to regulate BMP gradient formation during embryonic dorsal-ventral axis patterning...