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What's new in edition 47 part 5/5
September 2006
Updates for genes S-Z |
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Updates at previously included gene sites:
genes S-Z listed below
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Supernumerary limbs: Processing of the Drosophila hedgehog signaling effector Ci-155 to the repressor Ci-75 is mediated by direct binding to the SCF component Slimb
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Signaling by extracellular Hedgehog (Hh) molecules is crucial for the correct allocation of cell fates and patterns of cell proliferation in humans and other organisms. Responses to Hh are universally mediated by regulating the activity and the proteolysis of the Gli family of transcriptional activators such that they induce target genes only in the presence of Hh. In the absence of Hh, the sole Drosophila Gli homolog, Cubitus interruptus (Ci), undergoes partial proteolysis to Ci-75, which represses key Hh target genes. This processing requires phosphorylation of full-length Ci (Ci-155) by protein kinase A (PKA), casein kinase 1 (CK1), and glycogen synthase kinase 3 (GSK3), as well as the activity of Slimb. Slimb is homologous to vertebrate ß-TRCP1, which binds as part of an SCF (Skp1/Cullin1/F-box) complex to a defined phosphopeptide motif to target proteins for ubiquitination and subsequent proteolysis. Phosphorylation of Ci at the specific PKA, GSK-3, and CK1 sites required in vivo for partial proteolysis stimulates binding to Slimb in vitro. Furthermore, a consensus Slimb/ß-TRCP1 binding site from another protein can substitute for phosphorylated residues of Ci-155 to direct conversion to Ci-75 in vivo. From this, it is concluded that Slimb binds directly to phosphorylated Ci-155 to initiate processing to Ci-75. The phosphorylated motifs in Ci that are recognized by Slimb have been explored and some evidence is provided that silencing of Ci-155 by phosphorylation may involve more than binding to Slimb (Smelkinson, 2006).
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Suppressor of Hairless: Bre1 is required for Notch signaling and histone modification
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Notch signaling controls numerous cell fate decisions during animal development. These typically involve a Notch-mediated switch in transcription of target genes, although the details of this molecular mechanism are poorly understood. dBre1 has been identified as a nuclear component required cell autonomously for the expression of Notch target genes in Drosophila development. dBre1 affects the levels of Su(H) in imaginal disc cells, and it stimulates the Su(H)-mediated transcription of a Notch-specific reporter in transfected Drosophila cells. Strikingly, dBre1 mutant clones show much reduced levels of methylated lysine 4 on histone 3 (H3K4m), a chromatin mark that has been implicated in transcriptional activation. Thus, dBre1 is the functional homolog of yeast Bre1p, an E3 ubiquitin ligase required for the monoubiquitination of histone H2B and, indirectly, for H3K4 methylation. These results indicate that histone modification is critical for the transcription of Notch target genes (Bray, 2005).
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Suppressor of Hairless: Regulation of expression of Vg and establishment of the dorsoventral compartment boundary in the wing imaginal disc by Suppressor of Hairless
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The transcription factor Suppressor of Hairless [Su(H)] belongs to the CSL transcription factor family, the main transcriptional effector of the Notch-signaling pathway. Su(H) is the only family member in the Drosophila genome and should therefore be the main transcriptional effector of the Notch pathway in this species. Despite this fact, in many developmental situations, the phenotype caused by loss of function of Su(H) is too weak for a factor that is supposed to mediate most or all aspects of Notch signaling. One example is the Su(H) mutant phenotype during the development of the wing, that is weaker in comparison to other genes required for Notch signaling. Another example is the complete absence of a phenotype upon loss of Su(H) function during the formation of the dorsoventral (D/V) compartment boundary, although the Notch pathway is required for this process. Recent work has shown that Su(H)/CBF1 has a second function as a transcriptional repressor, in the absence of the activity of the Notch pathway. As a repressor, Su(H) acts in a complex together with Hairless (H), which acts as a bridge to recruit the co-repressors Groucho and CtBP, and acts in a Notch-independent manner to prevent the transcription of target genes. This raises the possibility that a de-repression of target genes can occur in the case of loss of function of Su(H). This study shows that the weak phenotype of Su(H) mutants during wing development and the absence of a phenotype during formation of the D/V compartment boundary are caused by the concomitant loss of the Notch-independent repressor function. This loss of the repressor function of Su(H) results in a de-repression of expression of target genes to a different degree in each process. Loss of Su(H) function during wing development results in a transient de-repression of expression of the selector gene vestigial (vg). This residual expression of vg is responsible for the weaker mutant phenotype of Su(H) in the wing. During the formation of the D/V compartment boundary, de-repression of target genes seems to be sufficiently strong, to compensate for the loss of Su(H) activity. Thus, de-repression of its target genes obscures the involvement of Su(H) in this process. Furthermore, evidence is provided that Dx does not signal in a Su(H)-independent manner as has been suggested previously (Koelzer, 2006).
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Suppressor of Hairy wing: Study of long-distance functional interactions between Su(Hw) insulators that can regulate enhancer-promoter communication
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The Su(Hw) insulator found in the gypsy retrotransposon is the most potent enhancer blocker in Drosophila melanogaster. However, two such insulators in tandem do not prevent enhancer-promoter communication, apparently because of their pairing interaction that results in mutual neutralization. Furthering studies of the role of insulators in the control of gene expression, this study presents a functional analysis of a large set of transgenic constructs with various arrangements of regulatory elements, including two or three insulators. Their interplay can have quite different outcomes depending on the order of and distance between elements. Thus, insulators can interact with each other over considerable distances, across interposed enhancers or promoters and coding sequences, whereby enhancer blocking may be attenuated, cancelled, or restored. Some inferences concerning the possible modes of insulator action are made from collating the new data and the relevant literature, with tentative schemes illustrating the regulatory situations in particular model constructs (Savitskaya, 2006).
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Syntaxin 1a: Rolling blackout shows a genetic interaction with syntaxin and is required for synaptic vesicle exocytosis
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Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate–diacylglycerol signaling in Drosophila neurons. Conditional temperature-sensitive (TS) rbo mutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, and rbo TS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adult rbo TS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction between rbo and syntaxin1A TS mutants, suggesting that RBO is required in the mechanism of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. The rbo TS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. It is concluded that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion (Huang, 2006).
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TGF-ß activated kinase 1: Drosophila TAB2, through interaction with Tak1, is required for the immune activation of JNK and NF-kappaB
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The TAK1 plays a pivotal role in the innate immune response of Drosophila by controlling the activation of JNK and NF-kappaB. Activation of TAK1 in mammals is mediated by two TAK1-binding proteins, TAB1 and TAB2, but the role of the TAB proteins in the immune response of Drosophila has not yet been established. A TAB2-like protein has been identified in Drosophila called dTAB2. Similar to mammalian TAB2/3, dTAB2 contains a ubiquitin-binding domain (N-CUE) at its N-terminal, and a highly conserved Zinc Finger (ZnF) domain at its C-terminal, respectively. dTAB2 can interact with TAK1, and stimulate the activation of the JNK and NF-kappaB signaling pathway. Furthermore, silencing of dTAB2 expression by dsRNAi inhibits JNK activation by peptidoglycans (PGN), but not by NaCl or sorbitol. In addition, suppression of dTAB2 blocks PGN-induced expression of antibacterial peptide genes, a function normally mediated by the activation of NF-kappaB signaling pathway. No significant effect on p38 activation by dTAB2 was found. These results suggest that dTAB2 is specifically required for PGN-induced activation of JNK and NF-kappaB signaling pathways (Zhuang, 2006).
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Timeless: Jetlag resets the Drosophila circadian clock by promoting light-induced degradation of Timeless
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Organisms ranging from bacteria to humans synchronize their internal clocks to daily cycles of light and dark. Photic entrainment of the Drosophila clock is mediated by proteasomal degradation of the clock protein Timeless. Mutations have been indentified in jetlag (CG8873: a gene coding for an F-box protein with leucine-rich repeats) that result in reduced light sensitivity of the circadian clock. Mutant flies show rhythmic behavior in constant light, reduced phase shifts in response to light pulses, and reduced light-dependent degradation of Tim. Expression of Jet along with the circadian photoreceptor cryptochrome (Cry) in cultured S2R cells confers light-dependent degradation onto Tim, thereby reconstituting the acute positive response of the circadian clock to light in a cell culture system. These results suggest that Jet is essential for resetting the clock by transmitting light signals from Cry to Tim (Koh, 2006).
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Tout-velu: Heparan sulfate polymerization in Drosophila: Ttv has GlcNAcT-II and GlcAT-II activities required for the biosynthesis of repeating disaccharide units of the HS backbone
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The formation of heparan sulfate (HS) chains is catalyzed by glycosyltransferases encoded by EXT (hereditary multiple exostosin gene) family members. Genetic screening for mutations affecting morphogen signaling pathways in Drosophila has identified three genes, tout-velu (ttv), sister of tout-velu (sotv), and brother of toutvelu (botv), which encode, respectively, homologues of human EXT1, EXT2, and EXTL3. So far, in vitro glycosyltransferase activities have been demonstrated only for Botv/DEXTL3, which harbors both N-acetylglucosaminyltransferase-I (GlcNAcT-I) and N-acetylglucosaminyltransferase-II (GlcNAcT-II) activities responsible for the chain initiation and elongation of HS, and no glucuronyltransferase-II (GlcAT-II) activity. This study demonstrates that Ttv/DEXT1 and Sotv/DEXT2 have GlcNAcT-II and GlcAT-II activities required for the biosynthesis of repeating disaccharide units of the HS backbone, and the coexpression of Ttv with Sotv markedly augment both glycosyltransferase activities when compared with the expression of Ttv or Sotv alone. Moreover, the polymerization of HS was demonstrated on a linkage region analogue as an acceptor substrate by Botv and an enzyme complex composed of Ttv and Sotv (Ttv-Sotv). In contrast to human, Drosophila Ttv-Sotv exhibit no GlcNAcT-I activity, indicating that Botv/DEXT3, which is an EXT-Like gene and possesses GlcNAcT-I activity required for the initiation of HS, is indispensable for the biosynthesis of HS chains in Drosophila. Thus, all three EXT members in Drosophila, Ttv, Sotv, and Botv, are required for the biosynthesis of full-length HS in Drosophila (Izumikawa, 2006).
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Ventral veins lacking: ventral veins lacking is required for specification of the tritocerebrum in embryonic brain development of Drosophila
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The homeotic or Hox genes encode a network of conserved transcription factors which provide axial positional information and control segment morphology in development and evolution. During embryonic brain development of Drosophila, the Hox gene labial (lab) is essential for tritocerebral neuromere specification; lab loss of function results in tritocerebral cells that fail to adopt a neuronal identity, causing axonal pathfinding defects. Evidence is presented that the POU-homeodomain DNA-binding protein ventral veins lacking (vvl) acts genetically downstream of lab in the specification of the tritocerebral neuromere. In the embryonic brain, vvl expression is seen in all brain neuromeres, including the tritocerebral lab domain. Lab mutant analysis shows that vvl expression in the tritocerebrum is dependent on lab activity. Loss-of-function analysis focussed on the tritocerebrum reveals that inactivation of vvl results in patterning defects that are comparable to the brain phenotype caused by null mutation of lab. In the absence of vvl, mutant tritocerebral cells are generated and positioned correctly, but these cells fail to express neuronal markers. This indicates defects in neuronal differentiation. Moreover, longitudinal axon pathways in the tritocerebrum are severely reduced or absent and the tritocerebral commissure is missing in the vvl mutant brain. Genetic rescue experiments show that vvl is able to partially replace lab in the specification of the tritocerebral neuromere. These results indicate that vvl acts downstream of the Hox gene lab and regulates specific aspects of neuronal differentiation within the tritocerebral neuromere during embryonic brain development of Drosophila (Meier, 2006).
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Wingless: Association of tracheal placodes with leg primordia in Drosophila and implications for the origin of insect tracheal systems
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Adaptation to diverse habitats has prompted the development of distinct
organs in different animals to better exploit their living conditions. This is
the case for the respiratory organs of arthropods, ranging from tracheae in
terrestrial insects to gills in aquatic crustaceans. Although
Drosophila tracheal development has been studied extensively, the
origin of the tracheal system has been a long-standing mystery. Tracheal placodes and leg primordia arise from a common pool of cells in
Drosophila, with differences in their fate controlled by the
activation state of the wingless signalling pathway. Early events that trigger leg specification have been elucidated and it is shown
that cryptic appendage primordia are associated with the tracheal placodes
even in abdominal segments. The association between tracheal and appendage
primordia in Drosophila is reminiscent of the association between
gills and appendages in crustaceans. This similarity is strengthened by the
finding that homologues of tracheal inducer genes are specifically expressed
in the gills of crustaceans. It is concluded that crustacean gills and insect
tracheae share a number of features that raise the possibility of an
evolutionary relationship between these structures. An evolutionary
scenario is proposed that accommodates the available data (Franch-Marro, 2006).
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Zn finger homeodomain 1: Zfh1, a somatic motor neuron transcription factor, regulates axon exit from the CNS
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Motor neurons are defined by their axon projections, which exit the CNS to innervate somatic or visceral musculature, yet remarkably little is known about how motor axons are programmed to exit the CNS. This study describes the role of the Drosophila Zfh1 transcription factor in promoting axon exit from the CNS. Zfh1 is detected in all embryonic somatic motor neurons, glia associated with the CNS surface and motor axons, and one identified interneuron. In zfh1 mutants, ventral projecting motor axons often stall at the edge of the CNS, failing to enter the muscle field, despite having normal motor neuron identity. Conversely, ectopic Zfh1 induces a subset of interneurons -- all normally expressing two or more 'ventral motor neuron transcription factors' (e.g., Islet, Hb9, Nkx6, Lim3) -- to project laterally and exit the CNS. It is concluded that Zfh1 is required for ventral motor axon exit from the CNS (Layden, 2006).
- What's new in edition 47 of the Interactive Fly:
- part 1/5 new genes |
updates: part 2/5 genes A-E | part 3/5 genes F-M | part 4/5 genes N-R
date revised: 10 September 2006
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