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• W1968136385 abstract "Article28 October 2004free access Capicua integrates input from two maternal systems in Drosophila terminal patterning Einat Cinnamon Einat Cinnamon Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Devorah Gur-Wahnon Devorah Gur-Wahnon Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Aharon Helman Aharon Helman Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Daniel St Johnston Daniel St Johnston The Gurdon Institute, Cambridge, UK Search for more papers by this author Gerardo Jiménez Gerardo Jiménez Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i Estudis Avançats, Parc Científic de Barcelona, Barcelona, Spain Search for more papers by this author Ze'ev Paroush Corresponding Author Ze'ev Paroush Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Einat Cinnamon Einat Cinnamon Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Devorah Gur-Wahnon Devorah Gur-Wahnon Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Aharon Helman Aharon Helman Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Daniel St Johnston Daniel St Johnston The Gurdon Institute, Cambridge, UK Search for more papers by this author Gerardo Jiménez Gerardo Jiménez Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i Estudis Avançats, Parc Científic de Barcelona, Barcelona, Spain Search for more papers by this author Ze'ev Paroush Corresponding Author Ze'ev Paroush Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel Search for more papers by this author Author Information Einat Cinnamon1,‡, Devorah Gur-Wahnon1,‡, Aharon Helman1, Daniel St Johnston2, Gerardo Jiménez3 and Ze'ev Paroush 1 1Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, Jerusalem, Israel 2The Gurdon Institute, Cambridge, UK 3Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i Estudis Avançats, Parc Científic de Barcelona, Barcelona, Spain ‡These authors contributed equally to this work *Corresponding author. Department of Biochemistry, Faculty of Medicine, Hadassah Medical School, The Hebrew University, PO Box 12272, Jerusalem 91120, Israel. Tel.: +972 2 6758 308; Fax: +972 2 6757 379; E-mail: [email protected] The EMBO Journal (2004)23:4571-4582https://doi.org/10.1038/sj.emboj.7600457 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info In Drosophila, the maternal terminal system specifies cell fates at the embryonic poles via the localised stimulation of the Torso receptor tyrosine kinase (RTK). Signalling by the Torso pathway relieves repression mediated by the Capicua and Groucho repressors, allowing the restricted expression of the zygotic terminal gap genes tailless and huckebein. Here we report a novel positive input into tailless and huckebein transcription by maternal posterior group genes, previously implicated in abdomen and pole cell formation. We show that absence of a subset of posterior group genes, or their overactivation, leads to the spatial reduction or expansion of the tailless and huckebein posterior expression domains, respectively. We demonstrate that the terminal and posterior systems converge, and that exclusion of Capicua from the termini of posterior group mutants is ineffective, accounting for reduced terminal gap gene expression in these embryos. We propose that the terminal and posterior systems function coordinately to alleviate transcriptional silencing by Capicua, and that the posterior system fine-tunes Torso RTK signalling output, ensuring precise spatial domains of tailless and huckebein expression. Introduction In the Drosophila embryo, four maternal coordinate systems act to specify distinct cell fates along the anteroposterior (A/P) and dorsoventral (D/V) axes: the anterior, posterior, D/V and terminal systems. The head and thorax are patterned by the activity of the anterior bicoid (bcd) morphogen, while abdomen formation is directed by a reciprocal posterior gradient of Nanos (Nos). Asymmetrical nuclear distribution of Dorsal governs D/V axis formation, whereas the nonsegmented termini are patterned by the terminal system. The activities of these systems induce regional-specific transcription of zygotic downstream target genes, the products of which eventually assign the different body parts with their prospective identities (St Johnston and Nusslein Volhard, 1992). Zygotic transcription in the termini of the embryo is controlled by the terminal system. A key component of this system is the gene torso (tor), which encodes a receptor tyrosine kinase (RTK) (Sprenger et al, 1989; St Johnston and Nusslein Volhard, 1992; Lu et al, 1993; Duffy and Perrimon, 1994). The Torso (Tor) receptor is uniformly distributed throughout the plasma membrane of the early embryo, but is activated only at the poles by a locally processed ligand, where it transmits a signal via the canonical Ras/Raf/MAP-kinase (MAPK) effectors (Casanova and Struhl, 1989, 1993; Sprenger and Nusslein Volhard, 1992; Lu et al, 1993; Duffy and Perrimon, 1994; Casali and Casanova, 2001; Furriols and Casanova, 2003). This signal leads to the restricted expression of two zygotic terminal gap genes, tailless (tll) and huckebein (hkb), at the poles of the embryo. tll and hkb encode transcription factors that, in turn, implement head and tail differentiation programmes (Strecker et al, 1986, 1988; Casanova, 1990; Pignoni et al, 1990; Weigel et al, 1990; Brönner and Jackle, 1991; Brönner et al, 1994; Furriols and Casanova, 2003). Genetic and molecular studies suggest that the activation of tll and hkb expression by the Tor pathway is indirect, and that Tor signalling allows regional expression of the terminal gap genes by counteracting, at the embryonic poles, general transcriptional repressors (Liaw et al, 1995; Paroush et al, 1997; Jiménez et al, 2000). Two major lines of evidence support this idea. First, a detailed analysis of the tll promoter has defined negative cis-acting regulatory sequences (designated Torso-response elements; TREs), whose deletion leads to ectopic expression throughout the embryo, indicating that tll is normally repressed outside the embryonic poles (Liaw et al, 1995; Rudolph et al, 1997). Second, mutations in genes encoding maternally contributed transcriptional repressors, such as the nuclear HMG-box protein Capicua (Cic) (Jiménez et al, 2000) and the global developmental corepressor Groucho (Gro), result in ectopic, more central, tll and hkb expression, even in the absence of functional Tor signalling (Paroush et al, 1994, 1997; Chen and Courey, 2000). How these factors regulate tll and hkb transcription is not well understood, although it appears that Cic is one of the key elements regulated by the Tor pathway (Jiménez et al, 2000). At the posterior of the embryo, the activity zone of the terminal system overlaps with that of the posterior system. Posterior group members are localised to the posterior pole, where they function in polar granule assembly and in the formation of the abdomen and germ cells (St Johnston and Nusslein Volhard, 1992). Assembly of the germ plasm occurs in a stepwise manner, with oskar (osk) being the key element of this process (Rongo and Lehmann, 1996). Embryos lacking maternal osk activity fail to form pole cells and to develop abdominal structures. Further, osk dosage dictates the amount of pole plasm assembled, and the consequent number of germ cells produced. Following translation of osk mRNA, the Osk protein localises the Vasa (Vas) DEAD-box RNA-binding helicase and the Tudor (Tud) protein to the posterior pole. These three proteins are then required for the execution of all posterior system functions. Downstream of Tud, the posterior group bifurcates: the product of the germ-cell-less (gcl) gene is required only for pole cell formation, whereas those of nanos (nos) and pumilio (pum) regulate abdomen formation by blocking translation of the anterior determinant hunchback (hb) (Rongo and Lehmann, 1996). In general, the distinct maternal genetic systems act independently of each other to define discrete portions of the embryonic pattern. Mutations in one maternal coordinate system seem to eliminate a specific body part without grossly affecting the rest of the embryonic pattern. Previous studies, however, have revealed interactions between the anterior, terminal and D/V systems at the most anterior region of the embryo (Pignoni et al, 1992; Liaw and Lengyel, 1993). At the posterior pole, on the other hand, the terminal system has long been thought to act alone in regulating zygotic terminal gap gene transcription, given that expression of tll and hkb is completely absent in embryos devoid of maternal tor activity, or lacking any other constituent of this signalling cascade (Weigel et al, 1990; Brönner and Jackle, 1991). In this work, we identify a surprising, novel role for maternal posterior group genes in embryonic terminal patterning. We show that tll and hkb expression patterns are spatially reduced in several posterior group mutants, suggesting that posterior group members positively contribute to the transcription of zygotic terminal gap genes. Our data indicate that the positive input from posterior group genes, in particular Nos, into tll and hkb expression converges on the Tor pathway. Thus, minimal TRE sequences, through which terminal system effectors regulate tll expression, also respond to the lack, or to the overactivation, of the posterior system. We further demonstrate that posterior genes act upstream or at the level of Cic, as ectopic accumulation of the Cic repressor is seen in the termini of posterior group mutants, accounting for the reduced tll and hkb expression domains in these embryos. Hence, multiple maternal inputs are required to effectively antagonise ubiquitous negative regulators at the posterior pole, in order to generate the precise patterns of tll and hkb expression. We propose that the posterior system acts to refine Tor RTK signalling output, ensuring that terminal gap gene expression patterns are properly established and consequently cell fates are correctly specified. Results Terminal gap gene expression is reduced in oskar, vasa and tudor mutant embryos By the beginning of cellularisation, tll and hkb are expressed in a nested-set pattern at the pole regions of wild-type Drosophila embryos (Weigel et al, 1990; Brönner et al, 1994). At this developmental stage, the dynamic tll RNA expression pattern has resolved into smaller domains at both the anterior and posterior ends. tll is expressed at the anterior cap in a horseshoe-shaped stripe that extends about two-thirds down along the D/V axis, whereas, posteriorly, tll covers a region comprising approximately 0–16% egg length (EL; 0% being the coordinate of the posterior tip) (Figure 1A) (Pignoni et al, 1990). hkb, on the other hand, is transcribed in the presumptive head region as a cap and, at the posterior, its expression domain overlaps with that of tll, covering about 0–12% EL (Figure 1E) (Brönner and Jackle, 1991). Figure 1.Terminal gap gene expression domains are reduced in oskar and tudor mutant embryos. Spatial distribution of tll (A–D) and hkb (E–H) transcripts in wild-type (A, E) and in posterior group mutant embryos (B–D, F–H), detected by in situ hybridisation as described in Materials and methods. Embryos shown are at the syncytial blastoderm stage (stage 4), and are derived from the following females: (A, E) wild type; (B) osk166/osk166; (F) osk346/osk346; (C, G) osk54/Df(3R)p-XT103; (D, H) tudWC/tudB36. Note the reduced posterior tll and hkb expression domains in osk and tud mutants, compared to wild-type embryos. The anterior expression domains of tll and hkb are also affected by the absence of osk (B, C, F, G), tud (D, H) and vasa (not shown) (see Discussion). For quantification of the spatial extent of the posterior terminal gap gene expression domains in these and other mutants, see Table I. Control and mutant embryos were mixed, then fixed and stained simultaneously. In all figures, the views are lateral, anterior is to the left and dorsal side up. Download figure Download PowerPoint We find that the posterior expression domains of both terminal gap genes are reduced in embryos laid by osk mutant females (Figure 1). Thus, tll and hkb expression is spatially reduced in stage 4 embryos derived from osk166 and osk346 homozygous females, and from null osk54/Df(3R)p-XT103 mutant females (Figure 1B, C, F and G; Table I). Retracted terminal gap gene expression domains are also seen in older, stage 5 embryos (not shown). In these and subsequent experiments, we minimised the effects caused by differential probe concentrations and/or duration of staining reactions by first mixing and then simultaneously fixing and processing wild-type embryos together with mutants, the latter distinguishable by their lack of pole cells. In all cases, the spatial reduction is reproducible and statistically significant (Table I). Thus, we conclude that the posterior group gene osk is required for the full extent of terminal gap gene expression at the posterior pole. Table 1. Extent of posterior tailless and huckebein expression domains in posterior group mutants Maternal genotype tailless huckebein Stage 4 Stage 5 Stage 4 Stage 5 osk166/osk166 0.82*** ND ND ND osk54/Df(3R)p-XT103 0.74*** 0.61*** 0.78** 0.85*** vasPD/vas011 0.88** ND ND ND tudWC/tudB36 0.61*** 0.66*** 1.05 1.07 nosL7/nosL7 0.89 0.96 ND ND nosBN/nosBN 0.72*** 0.83* 0.93 0.84* nosRC/nosBN 0.58*** 0.71*** 0.52*** 0.80*** pum680/pum680 1.26*** 1.04 ND ND pumET1/In(3R)Msc 0.99 0.98 1.24** 1.02 gclΔ49/gclΔ49 0.94 1.04 1.19* 1.18*** oskAk/oskAk (4xosk) 1.75*** 1.07 1.34** 1.45*** bicS/bicS 1.39*** 1.63*** 1.39*** ND Values below or above 1 represent a reduction or expansion of gap gene expression domains, respectively, while ratios of around 1 denote normal extent (see Materials and methods). ND: not determined. Statistically significant results are marked by asterisks: ***P<0.01, **P<0.05 and *P<0.1. We also examined if mutations in other posterior group genes elicit similar alterations in terminal gap gene patterns. The vasa (vas) gene product is required for the activation of Osk translation (Rongo et al, 1995). We find that vasPD/vas011 mutant embryos show a reduction in tll and hkb expression, comparable to that seen in osk mutants (data not shown; Table I), implying that, like osk, vas also normally contributes to terminal gap gene regulation. Next we examined the effect of Tud, a posterior group member that mediates the transport of RNA from the mitochondria to polar granules (Amikura et al, 2001). In embryos derived from tudWC/tudB36 mothers, the posterior tll expression domain is reduced, although hkb expression is not significantly altered, perhaps due to the use of hypomorphic alleles (Figure 1D and H; Table I). In all of the above mutant backgrounds, a lower staining intensity relative to that seen in wild-type embryos (Figure 1) suggests a decline in transcript abundance. This weakened staining is specific to tll and hkb transcripts, as other genes are expressed at normal levels in the posterior and elsewhere of osk mutant embryos (D Gur-Wahnon, unpublished results). Notably, the anterior tll expression domain is also reduced in all of the above posterior group mutants (see Discussion). Thus, the posterior group genes osk, vasa and tud are positively required for the expression of the terminal gap genes tll and hkb. Nanos positively regulates tailless and huckebein expression We next established the expression patterns of tll and hkb in embryos mutant for posterior genes acting downstream of osk, vas and tud (Figure 5I) (Rongo and Lehmann, 1996). In embryos produced by gcl homozygous mothers, the tll and hkb expression domains are both normal (data not shown; Table I), suggesting that gcl is not required for terminal gap gene regulation. Given that pole cells do not form in gcl mutants (Jongens et al, 1992), we conclude that the lack of germ cells in osk, vas and tud embryos is not the basis for the reduced tll and hkb expression in these genotypes. Embryos derived from nos and pum mutant mothers possess pole cells, but exhibit abdominal defects resulting from the failure of these RNA-binding proteins to repress the translation of maternal hb. We find that Nos participates in tll and hkb regulation. In stage 4 embryos derived from nosRC/nosBN or homozygous nosBN mutant females, the tll and hkb expression domains are significantly reduced (Figure 2B and E; data not shown; Table I), implying that the Nos protein is a positive regulator of terminal gap gene expression. Double in situ hybridisation staining shows that the posterior expression of tll, but not that of the central Krüppel (Kr) stripe, is reduced in nosRC/nosBN embryos compared to wild type (Figure 2M and N), confirming the specificity of this effect. In contrast, we find that pumET1/In(3R)Msc females lay embryos with normal tll and hkb expression (Figure 2C and F; Table I), indicating that pum may not be involved in this regulation. Figure 2.Terminal gap gene expression domains are reduced in nanos but not in pumilio mutants. (A–I, M, N) In situ hybridisation. (J–L) Larval cuticular preparations. (A, D, G, J, M) Wild type; (B, E, H, K, N) nosRC/nosBN; (C, F, I, L) pumET1/In(3R)Msc. Expression domains of tll (A–C), hkb (D–F), gt (G–I) and tll+Kr (M, N) in stage 4 embryos. Note that the posterior tll and hkb expression domains are reduced in nos, but not in pum, mutant embryos. In both nos and pum mutants, abdominal segmentation is defective, as evident by the absence of the posterior giant stripe (H, I; cf. with G) and by the lack of abdominal denticle belts (K, L; cf. with J). The Kr stripe expands posteriorly in nos (cf. N with M) and osk mutant embryos (not shown) (Hulskamp et al, 1990). Download figure Download PowerPoint The differential effects of Nos and Pum on tll and hkb expression are surprising, given that these two proteins act as partners in abdominal patterning and in other settings. However, two lines of evidence support this conclusion. First, the mutant nos and pum allelic combinations tested show a similar loss of posterior denticle belts (Figure 2K and L) (Irish et al, 1989; Murata and Wharton, 1995) and the absence of abdominal gap gene expression (e.g., the posterior giant stripe; Figure 2H and I), as reported for posterior group mutants (Kraut and Levine, 1991). Second, we find that tll and hkb expression is unaffected in homozygous nosL7 mutant embryos (Table I). This particular allele encodes a Nos protein lacking its carboxy-terminal tail, the domain required for the recruitment of Nos into the Pum/hb mRNA ternary complex (Sonoda and Wharton, 1999). Thus, nosL7 renders Nos inactive as a repressor of hb mRNA translation (a Pum-dependent activity), yet it does not impair Nos' other functions, for example in oogenesis (Arrizabalaga and Lehmann, 1999). Nos could therefore be acting in terminal patterning in conjunction with some other maternally provided factor, perhaps an RNA-binding protein. Given that the pumET1/In(3R)Msc trans-allelic combination might still possess some Pum activity, however, it is premature to completely rule out Pum's contribution to terminal gap gene regulation. Taken together, our results suggest that Nos is a key posterior group member required for accurate terminal gap gene expression. Overexpression of oskar or nanos leads to expanded terminal gap gene expression If posterior group genes have a positive input into terminal gap gene regulation, then the overexpression of these genes should cause broadening of the tll and hkb posterior expression domains. To test this idea, terminal gap gene expression patterns were assessed in offsprings of females with increased osk dosage, or that uniformly express nos. Embryos overexpressing osk were derived from two maternal genetic backgrounds, each containing two extra copies of osk: homozygous females, which harbour a small tandem duplication of the osk locus (referred to herein as bicaudalS; bicS), and homozygous females carrying an osk transgene (4xosk females) (Ephrussi and Lehmann, 1992). To express nos uniformly, we used a nos transgene, in which the nos 3′UTR was replaced with that of tubulin (Gavis and Lehmann, 1994). In all cases, embryos show cuticular phenotypes attributable to osk or nos overexpression: either a pronounced reduction of head structures, or a bicaudal appearance, with posterior terminal telson structures replacing the anterior acron (data not shown). Significantly, all combinations result in expanded posterior domains of tll and hkb (Figure 3; Table I), supporting the notion that osk, nos and other posterior group genes fulfil a positive role in terminal gap gene regulation. Figure 3.Overexpression of oskar or nanos leads to expanded terminal gap gene expression domains. Expression of tll (A–D) and hkb (E–H) in stage 4 embryos. Shown are embryos produced by the following females: (A, E) wild type; (B, F) homozygous Dp(3;3)bicS (bicS); (C, G) homozygous 4xosk; (D, H) heterozygous nos-tub3′UTR. Note the significant expansion of the tll and hkb posterior expression domains in lines overexpressing osk or nos. In these lines, the anterior tll stripe is also shifted. (I, J) Cuticular phenotypes of embryos produced by homozygous tsl (I) or bicS tsl double-mutant females (J). The arrow in (J) points to a partially restored filzkorper in a bicS tsl embryo, missing in a tsl mutant (I). Download figure Download PowerPoint Remarkably, overexpression of osk can rescue some of the morphological defects seen in terminal group mutants. Specifically, the terminal filzkorper (FK) structure is never observed in hypomorphic torso-like (tsl691) mutant embryos, but is partially rescued in embryos harbouring this allele that also concomitantly overexpress osk (bicS tsl; Figure 3I and J). Thus, overactivation of the posterior system appears to compensate in part for compromised terminal system activity. We note that the anterior tll stripe retracts anteriorly when osk or nos are overexpressed (Figure 3B–D), similar to what is seen in bcd mutants (Pignoni et al, 1992) (in both cases, anterior hkb expression does not change). This aspect of tll misexpression likely stems from translational inhibition of bcd mRNA by Nos, which is mislocalised to the anterior in these embryos (Ephrussi and Lehmann, 1992; Gavis and Lehmann, 1994). Posterior group genes regulate tailless at the transcriptional level None of the posterior group members encode for transcription factors, so we next asked whether the products of these genes regulate tll and hkb expression at the transcriptional level, or whether they do so post-transcriptionally, for example by stabilising terminal gap gene mRNA. To address this point, we made use of a reporter construct (P1), the expression of which is controlled by extensive tll promoter sequences and resembles that of the endogenous gene (Figure 4A) (Liaw and Lengyel, 1993). We find that P1 lacZ expression is reduced in osk mutants (Figure 4B), while it expands into central parts in embryos laid by females overexpressing osk (Figure 4C), in accordance with endogenous tll expression (Figures 1B and 3C). Moreover, the anterior P1 lacZ stripe is also affected in 4xosk embryos, similar to endogenous tll. Thus, the positive regulatory input from posterior group genes must be acting, presumably indirectly, on tll transcription rather than at a post-transcriptional level. Figure 4.Input by the posterior group converges on minimal TREs in the tailless promoter. (A–I) In situ hybridisation for lacZ reporter expression, driven by different tll promoter constructs, in stage 4 embryos: (A–C) P1, a 5.9 kb full-length tll promoter construct; (D–F) K11, tll promoter subregion −2291 to −2770, oligomerised four-fold; (G–I) G22, tll promoter subregion −324 to −200, oligomerised four-fold. (A, D, G) In a wild-type background, all constructs drive reporter expression in a posterior cap. The P1 and G22 constructs also drive expression in the anterior. Expansion of the lacZ expression pattern is apparent for all three constructs when osk is overexpressed (4xosk; C, F, I), while lacZ expression is significantly reduced for the P1 and K11 constructs, although not for G22, in osk166 homozygous flies (B, E, H). Download figure Download PowerPoint Figure 5.Posterior group genes feed into the Torso pathway upstream of Capicua. (A–D) Staining for dpERK (activated MAPK) at stage 4. (E–H) Distribution of the HA-tagged Cic protein (CicHA) at stage 4, revealed by anti-HA antibody staining. (A) Wild-type embryos; (B) embryos produced by osk54/Df(3R)p-XT103 mutant mothers; (C) embryos produced by 4xosk mothers; (D) embryos produced by torY9 mothers; (E) embryos derived from females heterozygous for the cicHA transgene (cicHA/+); (F) embryos produced by cicHA/+; nosRC/nosBN mothers; (G, H) larger magnifications of the posterior poles of the embryos shown in (E, F), respectively. The arrowheads in (G, H) indicate the same relative point in the two embryos. dpERK levels in osk and 4xosk mutants are identical to those seen in wild-type embryos; however note the ectopic accumulation of CicHA in the terminal regions of nos mutants compared to its exclusion from these regions in wild-type embryos. Note that while HA staining is observed to the left of the arrowhead in nos mutants (H), it is missing at the corresponding point in the wild type (G). (I) Schematic representation of the intersection between the posterior system and the Torso pathway. Nos acts with Pum or some unknown partner, at the level of MAPK or downstream to it, to downregulate the Cic repressor complex at the termini, facilitating tll and hkb transcription (see text for details). Posterior group members that are not involved in terminal gene regulation are presented in light grey. Download figure Download PowerPoint Torso-response elements in the tailless promoter respond to alterations in maternal oskar dosage We next investigated if posterior group genes act in parallel to, and independently of, the tor signalling cascade, or whether they feed into the terminal pathway. Molecular dissection of the tll promoter has defined two cis-acting TRE sequences that respond to both the lack and the constitutive activation of the tor pathway (Liaw et al, 1995). These DNA regulatory elements mediate transcriptional repression, specifically by the Cic repressor complex, as mutations in either the TREs or in cic lead to derepression (data not shown) (Liaw et al, 1995; Jiménez et al, 2000). We reasoned that if the posterior system regulates terminal gap gene expression independently of the Tor pathway, then its effects are likely to be exerted via distinct cis-acting elements in the tll promoter. If, on the other hand, this maternal system acts jointly with the terminal pathway, then input by the posterior system is expected to converge on the previously defined TREs. Transgenes containing the minimal distal (K11) and proximal (G22) TRE sequences drive lacZ expression in a tll-like posterior cap, although, as previously published, the intensity of expression is reduced when compared to that of the full-length tll promoter construct (P1), probably as a result of lost activator binding sites (Figure 4D and G; cf. with Figure 4A) (Liaw et al, 1995; Rudolph et al, 1997). We find that lacZ expression, driven by the distal TRE (K11), is reduced in osk mutants (Figure 4E) and expanded in 4xosk embryos (Figure 4F), similar to the P1 reporter. When driven by the proximal TRE (G22), lacZ expression also expands in response to osk overexpression, although it is not significantly reduced in an osk mutant background (Figure 4H and I; cf. with Figure 4G). Given that besides the minimal TREs there are no apparent sequences common to both constructs, it appears that posterior group genes act on the same elements in the tll promoter that mediate terminal system output. Input from posterior group genes intersects with the torso pathway upstream of Capicua To test at what level the crosstalk between the posterior and terminal systems occurs, we first monitored the phosphorylation state of MAPK when osk dosage is altered. The doubly phosphorylated form of MAPK (dpERK), which can be reliably detected using a specific antibody (Gabay et al, 1997a), makes a perfect read-out for signals transmitted by RTK pathways via the generic Ras/Raf/MAPK module, including that by the Tor receptor. Thus, MAPK activation is diminished in embryos derived from homozygous tsl mutant females, and is uniformly detected when tor is constitutively activated (Figure 5D) (Gabay et al, 1997b). In contrast, we find that t" @default.
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• W1968136385 title "Capicua integrates input from two maternal systems in Drosophila terminal patterning" @default.
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