Self-Regulatory Circuits in Dorsoventral Axis Formation of the Short-Germ Beetle Tribolium castaneum

Fonseca, Rodrigo Nunes da; Levetzow, Cornelia von; Kalscheuer, Patrick; Basal, Abidin; Zee, Maurijn van der; Roth, Siegfried

doi:10.1016/j.devcel.2008.02.011

Cited by 87 publications

(131 citation statements)

References 41 publications

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“…In light of this, we were particularly curious how the borders of these genes were reliably positioned. One possibility is that the Dorsal gradient is initially broader and then narrows as seen in the short germ beetle, Tribolium castaneum (20,21). However, our results dismiss this possibility by showing that there is little to no change in either the Gaussian shape or the extent of the Dorsal gradient during nc 10-14 (Fig.…”

Section: Discussioncontrasting

confidence: 53%

Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila

Liberman

Reeves

Stathopoulos

2009

Proc. Natl. Acad. Sci. U.S.A.

128

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The NF-B-related transcription factor, Dorsal, forms a nuclear concentration gradient in the early Drosophila embryo, patterning the dorsal-ventral (DV) axis to specify mesoderm, neurogenic ectoderm, and dorsal ectoderm cell fates. The concentration of nuclear Dorsal is thought to determine these patterning events; however, the levels of nuclear Dorsal have not been quantified previously. Furthermore, existing models of Dorsal-dependent germ layer specification and patterning consider steady-state levels of Dorsal relative to target gene expression patterns, yet both Dorsal gradient formation and gene expression are dynamic. We devised a quantitative imaging method to measure the Dorsal nuclear gradient while simultaneously examining Dorsal target gene expression along the DV axis. Unlike observations from other insects such as Tribolium, we find the Dorsal gradient maintains a constant bell-shaped distribution during embryogenesis. We also find that some classical Dorsal target genes are located outside the region of graded Dorsal nuclear localization, raising the question of whether these genes are direct Dorsal targets. Additionally, we show that Dorsal levels change in time during embryogenesis such that a steady state is not reached. These results suggest that the multiple gene expression outputs observed along the DV axis do not simply reflect a steady-state Dorsal nuclear gradient. Instead, we propose that the Dorsal gradient supplies positional information throughout nuclear cycles 10-14, providing additional evidence for the idea that compensatory combinatorial interactions between Dorsal and other factors effect differential gene expression along the DV axis.development ͉ gene expression T he morphogen gradient model describes how positional information is conferred to a field of cells, enabling the specification of different cell types. In this model, a diffusible molecule forms a concentration gradient that dictates differential gene expression in a concentration dependent fashion. Appealing in its simplicity, this concept has been used to explain cell-fate specification and patterning in animals (1).The NF-B homolog, Dorsal, is present in a nuclear concentration gradient within the Drosophila melanogaster embryo (reviewed in ref.2). The asymmetries that result in the Dorsal gradient are initialized in the egg before fertilization by Gurkendependent signaling. After fertilization, this DV information is relayed to the embryo through ventrally localized maturation of the Toll-receptor ligand, Spätzle. Toll activation directs the degradation of the IB homolog, Cactus, allowing Dorsal to enter the nucleus. Although the maternally deposited dorsal mRNA and the translated protein are initially uniform within the early embryo, nuclear import of Dorsal selectively occurs in ventral regions as a result of Toll activation, resulting in a nuclear concentration gradient that is first visible at nuclear cycle (nc) 10, when nuclei migrate to the periphery of the embryo. Using transgenic flies with a Dorsal-GFP fu...

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Section: Discussioncontrasting

confidence: 53%

Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila

Liberman

Reeves

Stathopoulos

2009

Proc. Natl. Acad. Sci. U.S.A.

128

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“…1A-C; Fig. S1H,I) (Nunes da Fonseca et al, 2008;van der Zee et al, 2006). One condition was used to produce severely ventralized embryos: Tc-dpp RNAi, which results in an expansion of the neuroectoderm at the expense of the dorsal ectoderm (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1). Furthermore, Tc-twi is downstream of Tc-Toll (Nunes da Fonseca et al, 2008). Therefore, we hoped to identify more direct targets of the early DV-GRN by focusing on the group of genes that are downregulated upon knockdown of both Tc-Toll and Tc-twi.…”

Section: Functional Analysis Of Neuroectodermal and Serosal Genesmentioning

confidence: 99%

“…For each knockdown, we analysed survival of the injected mothers, the morphology of DAPI-stained embryos and the expression of marker genes for DV cell specification: Tc-pannier (Tc-pnr, amnion; van der Zee et al, 2005), Tc-twi (mesoderm) and Tc-achaete-scute homolog (Tc-ash, neuronal precursors; Wheeler et al, 2003). Tcengrailed (Tc-en) and/or Tc-gooseberry (Tc-gsb) (Brown et al, 1994;Davis et al, 2001; Nunes da Fonseca et al, 2008) (Fig. S3) were used to monitor segmentation.…”

Section: Functional Analysis Of Neuroectodermal and Serosal Genesmentioning

confidence: 99%

“…The NF-κB/Dorsal gradient is initiated in a broad domain that then rapidly refines and disappears while the expression domains of potential target genes are established (Chen et al, 2000; Nunes da Fonseca et al, 2008). The number of genes controlled by Toll signalling in Tribolium appears to be reduced compared with Drosophila.…”

Section: Introductionmentioning

confidence: 99%

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Genome wide identification ofTriboliumdorsoventral patterning genes

et al. 2016

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The gene regulatory network controlling dorsoventral axis formation in insects has undergone drastic evolutionary changes. In Drosophila, a stable long-range gradient of Toll signalling specifies ventral cell fates and restricts BMP signalling to the dorsal half of the embryo. In Tribolium, however, Toll signalling is transient and only indirectly controls BMP signalling. In order to gain unbiased insights into the Tribolium network, we performed comparative transcriptome analyses of embryos with various dorsoventral pattering defects produced by parental RNAi for Toll and BMP signalling components. We also included embryos lacking the mesoderm ( produced by Tctwist RNAi) and characterized similarities and differences between Drosophila and Tribolium twist loss-of-function phenotypes. Using stringent conditions, we identified over 750 differentially expressed genes and analysed a subset with altered expression in more than one knockdown condition. We found new genes with localized expression and showed that conserved genes frequently possess earlier and stronger phenotypes than their Drosophila orthologues. For example, the leucine-rich repeat (LRR) protein Tartan, which has only a minor influence on nervous system development in Drosophila, is essential for early neurogenesis in Tribolium and the Tc-zinc-finger homeodomain protein 1 (Tc-zfh1), the orthologue of which plays a minor role in Drosophila muscle development, is essential for maintaining early Tc-twist expression, indicating an important function for mesoderm specification.

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Demographics of hepatitis C virus today†

Gonzalez

Davis

2012

Clinical Liver Disease

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Se estima que, en la actualidad, entre 3 y 4 millones de personas en Estados Unidos y Suprimir 170 millones en todo el mundo presentan una infecci on cr onica por el virus de la hepatitis C (VHC) 1-3 . El VHC sigue siendo la infecci on cr onica transmitida por la sangre que aparece con m as frecuencia en Estados Unidos, y supone hasta dos tercios de los nuevos casos diagnosticados de hepatopat a cr onica 3,4 . Como este virus se transmite principalmente por v a parenteral, sabemos que determinadas poblaciones presentan un mayor riesgo de exposici on: las personas que recibieron transfusiones de sangre antes de 1992 o factores de la coagulaci on antes de 1987, las que padecen hemofilia, los pacientes en hemodi alisis, los individuos infectados por el virus de la inmunodeficiencia humana (VIH) y las personas que utilizan drogas por v a intravenosa 5 . Estos grupos se incluyen por tanto en las recomendaciones actuales para identificar a los individuos que podr an beneficiarse de una detecci on precoz 5,6 (Tabla 1). Aunque dichas recomendaciones comenzaron a utilizarse hace m as de una d ecada, todav a se cuestiona si la estrategia que proponen ha resultado eficaz para identificar a los individuos con infecci on cr onica por el VHC, la mayor a de los cuales nacieron entre 1945 y 1964 3 . Una consideraci on adicional es que algunas de las poblaciones que presentan la mayor prevalencia del VHC (como las personas que utilizan drogas por v a intravenosa, los reclusos o los mendigos) podr an no tener acceso al sistema sanitario o no estar incluidas en los programas de vigilancia poblacional, por lo que la verdadera prevalencia del VHC podr a estar cambiar por subvalorada 1 . En Estados Unidos, el medio m as frecuente de transmisi on del VHC sigue siendo el uso de drogas por v a parenteral; la seroprevalencia de anticuerpos frente al VHC podr a ser superior al 70 % despu es de 3-5 años de exposici on habitual 7,8 (Figura 1). Los esfuerzos por implantar estrategias de prevenci on y tratamiento en esta poblaci on podr an ser cada vez m as importantes para controlar la aparici on de nuevas infecciones por el VHC.La importancia de contar con estrategias de detecci on eficaces se ha visto reforzada por la reciente disponibilidad de terapias antivirales, cada vez m as eficaces 9,10 . La consecuci on del aclaramiento viral a largo plazo despu es de un ciclo de terapia antiviral (lo que se conoce como «respuesta virol ogica sostenida»), es duradera, y demuestra que el VHC se puede erradicar con un tratamiento eficaz 11,12 . Adem as, un tratamiento cambiar por exitoso de la infecci on puede tener un gran impacto sobre la evoluci on natural de la hepatopat a cr onica asociada a este virus, dado que la consecuci on de una respuesta virol ogica sostenida podr a dar lugar a una importante disminuci on del riesgo de carcinoma hepatocelular (CHC) y de la mortalidad relacionada con cambiar por la enfermedad hep atica 13-17 . Aunque un paso importante para minimizar la carga global asociada a las infecciones por el VHC consiste en identifi...

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Self-Regulatory Circuits in Dorsoventral Axis Formation of the Short-Germ Beetle Tribolium castaneum

Cited by 87 publications

References 41 publications

Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila

Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila

Genome wide identification ofTriboliumdorsoventral patterning genes

Demographics of hepatitis C virus today†

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