Toll-1, EP1051, T1, dToll
transmembrane receptor - IL1 homolog - a crucial protein for embryonic dorsal/ventral polarity and immunity - receptor for spätzle - activates the Tl intracellular signaling pathway
Please see the GBrowse view of Dmel\Tl or the JBrowse view of Dmel\Tl for information on other features
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Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.47
gene_with_stop_codon_read_through ; SO:0000697
Stop-codon suppression (UAG) postulated; FBrf0216884.
Gene model reviewed during 5.44
Gene model reviewed during 5.49
5.3 (northern blot)
In the absence of ligand, forms a low-affinity disulfide-linked homodimer (PubMed:24733933). In the presence of ligand, crystal structures show one Tl molecule bound to a spaetzle C-106 homodimer (PubMed:24282309, PubMed:24733933). However, the active complex probably consists of two Tl molecules bound to a spaetzle C-106 homodimer (PubMed:24282309, PubMed:24733933). This is supported by in vitro experiments which also show binding of the spaetzle C-106 dimer to 2 Tl receptors (PubMed:12872120). Ligand binding induces conformational changes in the extracellular domain of Tl (PubMed:24282309). This may enable a secondary homodimerization interface at the C-terminus of the Tl extracellular domain (PubMed:24282309).
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Tl using the Feature Mapper tool.
Protein, which is maternally provide is observed in the area between the somatic bud on the plasma membrane prior to embryonic cycle 13. At cellularization during cycle 14 the protein becomes concentrated at the basal membrane.
Tl protein is absent in the earliest stages of embryonic development, begins to accumulate prior to nuclear migration and peaks in late syncytial blastoderm embryos.
GBrowse - Visual display of RNA-Seq signals
View Dmel\Tl in GBrowse 23-92
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Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
polyclonal
Source for merge of: Tl EP1051
dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
RNAi screen using dsRNA made from templates generated with primers directed against this gene causes a phenotype when assayed in Kc167 and S2R+ cells: binucleate cells.
Tl does not function as a pattern recognition receptor in the Drosophila host defence.
Tl acts in a cell autonomous manner in the fat body.
Expression of Tl in a subset of epidermal cells, including the epidermal muscle attachment cells, but not in the musculature is necessary for proper muscle development in the embryo.
Tl mRNA is translationally activated by regulated cytoplasmic polyadenylation.
Tl pathway is required for the nuclear import of dl in the immune response, but not required for the nuclear import of Dif. Cytoplasmic retention of both dl and Dif depends on cact protein. The two signalling pathways that target cact for degradation must discriminate between cact-dl and cact-Dif complexes.
A combination of genetic manipulation and single-cell visualisation demonstrates the timing and cell specificity of muscular Tl expression can affect synaptogenesis of RP3 and other motoneuron growth cones.
The embryonic regulatory pathway, comprising the gene products between spz and cact (Tl, tub and pll) but not the genes acting upstream or downstream (ea and dl), is involved in the induction of the Drs gene in adults. Mutations that affect the synthesis of antimicrobial peptides dramatically lower the resistance of flies to infection.
An activated processed form of spz can activate Tl when injected into the extracellular space of early embryos (FBrf0074384). cact is rapidly degraded in response to spz injection.
dl is an embryonic phosphoprotein and its phosphorylation state is regulated by an intracellular signaling pathway initiated by the transmembrane receptor Tl. Using a combined genetic and biochemical approach it is demonstrated that activation of Tl stimulates an increase in the extent of dl phosphorylation.
Dorsal-ventral patterning is regulated by a signalling pathway that includes Tl and transcription factors, dl, that interact with related enhancers, rho. The κ enhancer from mouse is capable of generating lateral stripes of Ecol\lacZ gene expression in transgenic embryos in a pattern similar to that directed by rho enhancer. Results suggest that enhancers can couple conserved signalling pathways to divergent gene functions, dorso-ventral patterning and mammalian haematopoiesis.
The spz product acts immediately upstream of Tl in dorso-ventral pattern formation in the embryo, and may encode the ligand that activates Tl. The secreted spz product must be activated by proteolytic cleavage, and localized proteolytic processing of the spz protein determines where the receptor, Tl, is active.
Comparisons of early development to that in other insects have revealed conservation of some aspects of development, as well as differences that may explain variations in early patterning events.
The Tl signalling pathway generates a dl nuclear gradient which initiates the differentiation of the mesoderm, neuroectoderm and dorsal ectoderm by activating and repressing gene expression in the early embryo. A second signalling pathway controlled by the tor receptor kinase also modulates dl activity.
Increased cytoplasmic calcium concentration and the expression of constitutively active Tl receptors can induce the relocalisation of dl in culture cells. Activation of endogenous Pka-C1, expression of wild type Tl receptors or treatment of cells with activators of Pkc53E and radical oxygen intermediates have only a marginal effects on the cellular distribution of dl protein.
Cytoplasmic injection studies indicate that the spatial information for the embryonic dorsal-ventral axis is largely derived from spatial cues in the extraembryonic compartment (most likely generated during oogenesis), which restrict the release of the putative Toll ligand. This ligand appears to originate from a ventrally restricted zone extending along the anterior-posterior axis, and its diffusion or graded release are required to determine the slope of the nuclear dorsal protein gradient. Both the Toll receptor and its ligand are in excess in wild type embryos.
Double mutant analysis indicates that ve acts upstream of Toll in dorsal-ventral axis formation, and the action of ve requires the grk-Egfr signaling pathway.
Double mutant combinations of Tl with ea alleles demonstrate that spatial regulation of ea activity by localized zymogen activation is a key initial event in defining the polarity of the dorsal-ventral embryonic pattern.
Toll enhances transport of dl protein into nucleus in cotransfected Schneider cells, perhaps via activated protein kinase A that phosphorylates dl gene product.
In addition to the Tl ligand, perivitelline fluid also contains three separate activities capable of rescuing ea, snk and spz. Serine proteolytic activity in the perivitelline fluid is required for the formation of the Tl ligand.
The cytoplasmic domain of the Tl protein is related to that of the human interleukin-1 receptor.
The properties of a peptide corresponding to residues 166-188 of the Tl protein have been studied in vitro.
The Tl protein is a glycoprotein which is tightly associated with embryonic membranes.
Recessive dorsalizing mutants of the dorsal group gene Tl have significantly reduced axial ratios in pupae.
Mutations in maternal dorsal class gene Tl do not interact with RpII140wimp.
Local activation of Tl by a Tl ligand initiates the formation of the dl nuclear concentration gradient, thereby determining the dorsoventral pattern.
The effects of an altered nucleocytoplasmic ratio on transcripts that normally undergo changes in transcript pattern in cell cycle 14 is studied. A delay in the maternal-to-zygotic transition of the dorsal-ventral polarity gene Tl is correlated with a decrease in nuclear density and a change in the cell cycle program.
Genetic and molecular analysis demonstrates that Tl is expressed and is functional zygotically as well as maternally.
Epistatic relationships exist between dorsalizing maternal effect mutations and "dppHin" alleles.
The expression of genes controlling neurogenesis is dependent on the previous activity of the genes controlling the development of the embryonic dorsal-ventral pattern. Double mutants N55e11 and Dl9P with Tl had neuralization of the entire ectoderm, a huge CNS and no epidermis as it had been substituted for by neural tissue.
Females carrying the dominant allele Tl3, when combined with the mutants gd, ndl, pip, snk, or ea, produce embryos that are lateralized like embryos derived from Tlrv8 females; these embryos lack dorsalmost and ventralmost pattern elements and have rings of denticles (Anderson, Jurgens and Nusslein-Volhard, 1985). Some alleles of ea increase the probability that the temperature-sensitive alleles Tlr5, Tlr6 and Tlr7 will survive. An interaction has been reported between the recessive allele Tlr7 and dpp (Irish and Gelbart, 1987). Double mutants of Tl3 and dl produce embryos that are completely dorsalized and indistinguishable from the embryos of dl homozygotes. Females carrying Tl2 or Tl4 in combination with gd, ndl, or dl also produce dorsalized embryos.
Maternal expression of the Toll gene is required for the normal production and distribution of positional information in the embryo (Anderson, Jurgens and Nusslein-Volhard, 1985; Anderson, Bokla and Nusslein-Volhard, 1985); zygotic expression is required to maintain viability in early larvae (Gerttula, Jin and Anderson, 1988). Toll mutants and deficiencies occurring in the mother result in lethal abnormalities in the pattern of gastrulation and the differentiation of cuticular structures in the offspring. When null alleles and deficiencies are homozygous in the zygote, delayed development and early lethality result. Females heterozygous for dominant Toll alleles are sterile, their lethal embryos being partially ventralized regardless of their genotype. Dorsoventral polarity is present; a furrow is formed in the midventral region, but the lateral cephalic fold is shifted to the dorsal side and the normal dorsal folds are missing. The cuticle lacks dorsal hairs, filzkorper, spiracles, head sensory organs and a head skeleton; there are patches of denticles extending around the entire dorsoventral circumference of the embryo (Anderson, Jurgens and Nusslein-Volhard, 1985). The ventral nervous system is also expanded (Campos-Ortega, 1983). Embryos produced by females hemizygous for some dominant alleles (Tl1/Df; Tl3/Df) are ventralized, but the embryos of other hemizygotes (Tl2/Df; Tl4/Df) are dorsalized, all cells behaving at gastrulation and in differentiation like wild-type dorsal cells. In embryos derived from Tl/+ females, virtually the entire ectoderm capable of neurogenesis in response to absence of Dl function (Campos-Ortega, 1983). Whereas females heterozygous for recessive alleles of Tl are fertile, homozygous Tl-recessive females are viable but sterile, their lethal embryos lacking dorsoventral polarity and forming no ventral furrow at gastrulation. In most recessive alleles (Tlr5, Tlr6, Tlr7), the embryos are partially dorsalized with laterally derived structures (Anderson, Jurgens and Nusslein-Volhard, 1985); for example, Tlr6 embryos differentiate dorsal hairs, filzkorper and ventral denticle bands of nearly normal width, but lack mesoderm (Anderson and Nusslein-Volhard, 1986). In one allele (Tlr4), however, embryos have no dorsal hairs and show rings of denticles as in TlD embryos (Anderson, Jurgens and Nusslein-Volhard, 1985). Hemizygotes for the Toll-recessives resemble the corresponding homozygotes in phenotype. A number of Toll alleles were obtained as reversions of the Toll-dominant phenotype. When crossed to wild-type males, females heterozygous for a null-type reversion are fully fertile; however, when crossed to males who are also heterozygous for a Toll null, these females produce Tl-homozygotes who are zygotic lethals, dying as early larvae and producing no Toll transcript. Heteroallelic combinations of reversions such as Tlrv1/Tlrv2 produce sterile females with lethal dorsalized embryos. Females carrying combinations of certain reversions and Toll-dominant (or Toll-recessive) alleles produce embryos with phenotypes like those of Toll-dominant (or Toll-recessive) hemizygotes. Most of the reversions, when in trans to deficiencies, result in females with dorsalized embryos, but a few hemizygous reversion females (Tlrv21, Tlrv22, Tlrv23) produce ventralized embryos (Hashimoto et al., 1988). The lethal embryos of Df(3R)Tl-X/Df(3R)ro-XB3 (null) females (Hashimoto, Hudson and Anderson, 1988), are completely dorsalized, never making ventral furrows, filzkorper, or denticles; their germ bands fail to extend; no Toll transcript is produced in these embryos except when contributed by wild-type fathers (Gerttula, Jin and Anderson, 1988). The 97D1-2 breakpoint of the Toll deficiency Df(3R)Tl-X maps within the 6.0 kb EcoRI fragment of a Toll clone (Hashimoto, Hudson and Anderson, 1988). Injection of wild-type cytoplasm into embryos of Toll-deficient females restores the wild-type dorsoventral pattern, the site of the injection determining the midventral part of the pattern (Anderson, Bokla and Nusslein-Volhard, 1985).
Wieschaus and Nusslein-Volhard.
