In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

We have previously shown that the member of the HES family hairy2 induces the ectopic expression of dorsal markers when it is overexpressed in the ventral side of Xenopus embryos. Intriguingly, hairy2 represses the mesoderm transcription factor brachyury (bra) throughout its domain in the marginal zone. Here we show that in early gastrula, bra and hairy2 are expressed in complementary domains. Overexpression of bra repressed hairy2. Interference of bra function with a dominant-negative construct expanded the hairy2 domain and, like hairy2 overexpression, promoted ectopic expression of dorsal axial markers in the ventral side and induced secondary axes without head and notochord. Hairy2 depletion rescued the ectopic dorsal development induced by interference of bra function. We concluded that an intact bra function is necessary to exclude hairy2 expression from the non-organiser field, to impede the ectopic specification of dorsal axial fates and the appearance of incomplete secondary axes. This evidence supports a previously unrecognised role for bra in maintaining the dorsal fates inhibited in the ventral marginal zone, preventing the appearance of trunk duplications.

In South America, the incorporation of genetically modified organisms (GMO) engineered to be resistant to pesticides changed the agricultural model into one dependent on the massive use of agrochemicals. Different pesticides are used in response to the demands of the global consuming market to control weeds, herbivorous arthropods, and crop diseases. Here, we review their effects on humans and animal models, in terms of genotoxicity, teratogenicity, and cell damage. We also stress the importance of biomarkers for medical surveillance of populations at risk and propose the use of biosensors as sensitive resources to detect undesirable effects of new molecules and environmental pollutants. The compatibility of glyphosate, the most intensively used herbicide associated to GMO crops, with an integrated pest management for soybean crops, is also discussed.

In South America, the incorporation of genetically modified organisms (GMO) engineered to be resistant to pesticides changed the agricultural model into one dependent on the massive use of agrochemicals. Different pesticides are used in response to the demands of the global consuming market to control weeds, herbivorous arthropods, and crop diseases. Here, we review their effects on humans and animal models, in terms of genotoxicity, teratogenicity, and cell damage. We also stress the importance of biomarkers for medical surveillance of populations at risk and propose the use of biosensors as sensitive resources to detect undesirable effects of new molecules and environmental pollutants. The compatibility of glyphosate, the most intensively used herbicide associated to GMO crops, with an integrated pest management for soybean crops, is also discussed.

The blastula chordin- and noggin-expressing centre (BCNE) is the predecessor of the Spemann-Mangold's organiser and also contains the precursors of the brain. This signalling centre comprises animal-dorsal and marginal-dorsal cells and appears as a consequence of the nuclear accumulation of β-catenin on the dorsal side. Here, we propose a role for Notch that was not previously explored during early development in vertebrates. Notch initially destabilises β-catenin in a process that does not depend on its phosphorylation by GSK3. This is important to restrict the BCNE to its normal extent and to control the size of the brain.

ADVERTISEMENT RETURN TO ISSUEPREVLetters to the Edito...Letters to the EditorNEXTReply to the Letter to the Editor Regarding Our Article (Paganelli et al., 2010)Andrés E. CarrascoView Author Information Universidad de Buenos AiresCite this: Chem. Res. Toxicol. 2011, 24, 5, 610–613Publication Date (Web):March 23, 2011Publication History Published online23 March 2011Published inissue 16 May 2011https://pubs.acs.org/doi/10.1021/tx200072khttps://doi.org/10.1021/tx200072kletterACS PublicationsCopyright © 2011 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1572Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (700 KB) Get e-AlertscloseSUBJECTS:Cell signaling,Organophosphorus compounds,Pest control,Safety,Toxicity Get e-Alerts

Editorial: Un futuro para la Argentina-A. Gak; 6- Vigencia del pensamiento latinoamericano en el campo CTS/S. Rietti; 14- El enfoque CTS para la ensenanza de las ciencias/A. Massarini; 20- Surgimiento, alienacion y retorno/D. Hurtado; 28- Para una nueva politica de ciencia y tecnologia/R. Dagnino; 36- Ciencia, universidad y economia/A. Langer; 46- El Estado: motor del desarrollo tecnologico/E. Dvorkin; 54- La extension tecnologica del INTI/E. Martinez; 60- Poder de compra del Estado/B. Cappra; 66- El principio precautorio en la ciencia Argentina/A. Carrasco; 72- Acerca del concepto de riesgo en ciencia y tecnologia/M. Albornoz; 78- Ciencia, tecnologia y etica/S. Rivera; 84- Ciencia y tecnologia en la mirada antropologica/A. Roca; 90- Politicas de CTI 96- La necesidad de una politica de Estado/M. Isturiz; 102- El sistema sociotecnico argentino/T. Buch; 110- La CyT en el marco de la economia ecologica/W. Pengue; 116- Ciencia, tecnologia y progreso social/J. C. Gottifredi; 122 Reportajes audiovisuales;

In vertebrates, the induction of the three germ layers (ectoderm, mesoderm and endoderm) has been extensively studied, but less is known about how they segregate. Here, we investigated whether Delta-Notch signaling is involved in this process. Activating the pathway in the marginal zone with Notch(ICD) resulted in an expansion of endodermal and neural ectoderm precursors, leaving a thinner mesodermal ring around the blastopore at gastrula stage, when germ layers are segregated. On the other hand, when the pathway was blocked with Delta-1(STU) or with an antisense morpholino oligonucleotide against Notch, the pan-mesodermal brachyury (bra) domain was expanded and the neural border was moved animalwards. Strikingly, the suprablastoporal endoderm was either expanded when Delta-1 signaling was blocked, or reduced after the general knock-down of Notch. In addition, either activating or blocking the pathway delays the blastopore closure. We conclude that the process of delimiting the three germ layers requires Notch signaling, which may be finely regulated by ligands and/or involve non-canonical components of the pathway. Moreover, Notch activity must be modulated at appropriate levels during this process in order to keep normal morphogenetic movements during gastrulation.

• ISAAA, a GM industry-supported group1 • Plant Research International at Wageningen University, the Netherlands, which has issued a paper presenting the arguments for the sustainability of GM RR soy2 • The Round Table on Responsible Soy (RTRS),3 a multi-stakeholder forum with a membership including NGOs such as WWF and Solidaridad and multinational companies such as ADM, Bunge, Cargill, Monsanto, Syngenta, Shell, and BP This report assesses the scientific and other documented evidence on GM RR soy and asks whether this definition is justified.

The broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior-posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.

Nonisotopic in situ hybridization using intact embryos or organs is an important method for determining the spatial distribution of RNAs. Because it allows the analysis of large numbers of samples, it is amenable to temporal expression studies and comparison between different genotypes. It offers sensitivity and reproducibility. In addition, histological details are not lost during the staining process. The protocols in this unit can be used for whole-mount in situ hybridization in Xenopus, mouse, and chicken embryos, as well as dissected organs from mouse and chicken. Preparation of digoxigenin-labeled riboprobes is also described.

Using in situ hybridization techniques with an RNA probe coding for approximately 3.5 repeats of ubiquitin, corresponding to the polyubiquitin genes, we were able to demonstrate that under normal conditions the expression of the ubiquitin genes predominates specially in regions CA1, CA2 and CA3 of the hippocampus, in the dentate gyrus and in Purkinje cells of the cerebellum, being less prominent in neuronal cell bodies of the cerebral cortex. When the animals were submitted to an acute oxidative stress by injection of Fe/Dextran, the hybridization signal was apparently increased in the above mentioned regions of the hippocampus and in the cerebral cortex. On the other hand, the animals chronically injected with Fe/Dextran showed a highly intense gene expression in the cerebral cortex and in the cerebellum, particularly in the granular cell layer of this structure. The hybridization signal of the transcripts was absent in the Purkinje cells. The results suggest that the expression of the ubiquitin genes by CNS neurons depends on the anatomical location of the cells and that it increases as a consequence of the oxidative stress conditions to which they are submitted.

Tissue distribution and localization of RNAs from the Xeb1 homoeo-box-containing gene were monitored with Northern blots and in situ hybridization. Xeb1 transcript distribution in larval stage embryos was established by blotting RNAs extracted from microdissected embryos. Those transcripts are restricted to a limited number of embryonic regions such as the dorsal trunk. The tissue/cell localization of Xeb1 transcripts was then monitored at several embryonic stages with in situ hybridization methods using [35S]RNA probes. These homoeo-box transcripts accumulated in a progressive and dynamic fashion. First localized in late gastrulae, they are distributed along the neural tube and in caudal mesoderm at later stages. By the swimming tadpole stage the spatial distribution of the homoeo-box transcripts is limited to specific regions of the central nervous system. Adult spinal cord shows the signal in specific neurons in the ventrolateral field of the gray matter.

Nine Trypanosoma cruzi isolates not examined previously for kDNA structure were characterized by (a) endonuclease restriction analysis of mini-circles, followed by agarose gel-electrophoresis of digests, and (b) hybridization of mini- and maxi-circle fragments with four 32P-labeled cloned mini-circles from T. cruzi (pTck-1, 12, 13 and 14) or with 32P-labeled maxi-circles from T. brucei, respectively. The gel electrophoresis patterns demonstrated significant differences between isolates, which were confirmed and extended by the hybridization assay. When using pTck-1 and pTck-12 as probes, widely distributed heterogeneous mini-circle subpopulations were demonstrated in all the examined isolates, despite the occurrence of extensive homologies. pTck-14, assayed under high stringent conditions, detected an almost homogeneous mini-circle subpopulation in only three isolates, although under relaxed conditions, pTck-14 shared sequence homologies with most of the mini-circle subpopulations from all isolates. Rapidly evolving mini-circle regions were also detected using as probe pTck-13, a small mini-circle fragment. Preliminary maxi-circle characterization revealed polymorphic restriction endonuclease sites in the different T. cruzi isolates. These results were consistent with those obtained with mini-circles subjected to the same treatment.