La Formació del cervell dels vertebrats, una telenovel·la?

El cervell dels vertebrats és tan complex que traçar-ne els orígens evolutius és problemàtic. Els estudis dels parents més propers als vertebrats, els ascidis i l'amfiox, mostraven que les proteïnes necessàries per formar aquest cervell eren exclusives dels vertebrats; ara bé, un nou article exposa que les bases gèniques d'aquesta estructura ja eren presents en branques més llunyanes de l'arbre evolutiu

A staging scheme for the development of the moth midge Clogmia albipunctata.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Model organisms, such as Drosophila melanogaster, allow us to address a wide range of biological questions with experimental rigour. However, studies in model species need to be complemented by comparative studies if we are to fully understand the functional properties and evolutionary history of developmental processes. The establishment of new model organisms is crucial for this purpose. One of the first essential steps to establish a species as an experimental model is to carefully describe its life cycle and development. The resulting staging scheme serves as a framework for molecular studies, and allows us to homologise developmental processes between species. In this paper, we have characterised the life cycle and development of an emerging non-drosophilid dipteran model system: the moth midge Clogmia albipunctata. In particular, we focus on early embryogenesis (cleavage and blastoderm cycles before gastrulation), on formation and retraction of extraembryonic tissues, and on formation of the germ line. Considering the large evolutionary distance between the two species (approximately 250 million years), we find that the development of C. albipunctata is remarkably conserved compared to D. melanogaster. On the other hand, we detect significant differences in morphology and timing affecting the development of extraembryonic tissues and the germ line. Moreover, C. albipunctata shows several heterochronic shifts, and lacks head involution and associated processes during late stages of development.The laboratory of Johannes Jaeger and this study in particular was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, by SGR grant 406 from the Catalan funding agency AGAUR, by grants BFU2009-10184 & BFU2012-33775 from the Spanish Ministry of Science (MICINN, now called MINECO), and by ERANet: ERASysBio+ grant EUI2009-04045 (MODHEART). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A staging scheme for the development of the scuttle fly Megaselia abdita

This is the final version of the article. Available from the publisher via the DOI in this record.Model organisms, such as Drosophila melanogaster, provide powerful experimental tools for the study of development. However, approaches using model systems need to be complemented by comparative studies for us to gain a deeper understanding of the functional properties and evolution of developmental processes. New model organisms need to be established to enable such comparative work. The establishment of new model system requires a detailed description of its life cycle and development. The resulting staging scheme is essential for providing morphological context for molecular studies, and allows us to homologise developmental processes between species. In this paper, we provide a staging scheme and morphological characterisation of the life cycle for an emerging non-drosophilid dipteran model system: the scuttle fly Megaselia abdita. We pay particular attention to early embryogenesis (cleavage and blastoderm stages up to gastrulation), the formation and retraction of extraembryonic tissues, and the determination and formation of germ (pole) cells. Despite the large evolutionary distance between the two species (approximately 150 million years), we find that M. abdita development is remarkably similar to D. melanogaster in terms of developmental landmarks and their relative timing.Funding: The laboratory of Johannes Jaeger and this study in particular was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, by SGR grant 406 from the Catalan funding agency AGAUR, by grants BFU2009-10184 & BFU2012-33775 from the Spanish Ministry of Science (MICINN, now called MINECO), and by ERANet: ERASysBio+ grant EUI2009-04045 (MODHEART). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Non-canonical dorsoventral patterning in the moth midge Clogmia albipunctata

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Bone morphogenetic proteins (BMPs) are of central importance for dorsal–ventral (DV) axis specification. They are core components of a signalling cascade that includes the BMP ligand decapentaplegic (DPP) and its antagonist short gastrulation (SOG) in Drosophila melanogaster. These components are very ancient, with orthologs involved in DV patterning in both protostomes and deuterostomes. Despite such strong conservation, recent comparative work in insects has revealed interesting differences in the way the patterning function of the DV system is achieved in different species. Results In this paper, we characterise the expression patterns of the principal components of the BMP DV patterning system, as well as its signalling outputs and downstream targets, in the non-cyclorrhaphan moth midge Clogmia albipunctata (Diptera: Psychodidae). We previously reported ventral expression patterns of dpp in the pole regions of C. albipunctata blastoderm embryos. Strikingly, we also find ventral sog and posteriorly restricted tkv expression, as well as expanded polar activity of pMad. We use our results from gene knock-down by embryonic RNA interference to propose a mechanism of polar morphogen shuttling in C. albipunctata. We compare these results to available data from other species and discuss scenarios for the evolution of DV signalling in the holometabolan insects. Conclusions A comparison of gene expression patterns across hemipteran and holometabolan insects reveals that expression of upstream signalling factors in the DV system is very variable, while signalling output is highly conserved. This has two major implications: first, as long as ligand shuttling and other upstream regulatory mechanisms lead to an appropriately localised activation of BMP signalling at the dorsal midline, it is of less importance exactly where the upstream components of the DV system are expressed. This, in turn, explains why the early-acting components of the DV patterning system in insects exhibit extensive amounts of developmental systems drift constrained by highly conserved downstream signalling output.This work was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, SGR Grant 406, from the Catalan funding agency AGAUR and by grants BFU2009-10184 and BFU2012-33775 from the Spanish Ministerio de Economia y Competitividad (MINECO). The Centre for Genomic Regulation (CRG) acknowledges support from MINECO, “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

Connective tissue is known to provide structural and functional 'glue' properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective tissue are minority or rare, but no less important than the nongenetic diseases. Here we review the impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin. It is important to consider that ROS and oxidative stress are not synonymous, although they are often closely linked. In a normal range, ROS have a relevant physiological role, whose levels result from a fine balance between ROS producers and ROS scavenge enzymatic systems. However, pathology arises or worsens when such balance is lost, like when ROS production is abnormally and constantly high and/or when ROS scavenge (enzymatic) systems are impaired. These concepts apply to numerous diseases, and connective tissue is no exception. We have organized this review around the two basic structural molecular components of connective tissue: The ground substance and fibers (collagen and elastic fibers)

A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila.

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.MINECO BFU2009-10184/BFU2012-33775/SEV-2012-0208 European Commission FP7/KBBE-2011/5/289434 La Caixa Savings Bank (PhD fellowship to BV) KLI Klosterneuburg (PhD Writing-up & Postdoctoral Fellowships to BV) Wissenschaftskolleg zu Berlin (Wiko) (Fellowships to JJ and AC

Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.

Published onlineJournal ArticleThis is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.Ministerio de Economía y Competitividad MEC/EMBL Agreement/ BFU2009-10184/ BFU2012-33775/ SEV-2012-0208 Agència de Gestió d'Ajuts Universitaris I de Recerca SGR Grant 406 European Commission FP7-KBBE-2011-5/289434 National Science Foundation IOS-0719445/IOS-112121

Comparative transcriptomics of early dipteran development.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). RESULTS: We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. CONCLUSIONS: We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies).Toni Hermoso Pulido from the CRG Bioinformatics Core provided help and support with the diptex database. We thank Debayan Datta, Maik Zehnsdorf, and Anna Menoyo (CRG Genomics Unit) for technical help. We gratefully acknowledge Urs Schmidt-Ott, for providing fly cultures, for sharing Episyrphus balteatus transcriptome data, for crucial advice on sequencing strategy, fly husbandry, and other experimental protocols, as well as for useful comments on the manuscript. Victor Jiménez-Guri drew the embryo pictures in Figure 1. This research was funded by the MEC/EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, by AGAUR SGR grant 406, and by Grants BFU2009-10184 and BFU2009-09168 from the Spanish Ministry of Science and Innovation (MICINN). EJG is supported by ERASysBio+ Grant P#161 (MODHEART). LC was supported by grant PTA2011-6729-I from the Spanish Ministry of Science and Innovation (MICINN). JHC is supported by a Juan de la Cierva postdoctoral fellowship from the Spanish Ministry of Science and Innovation (JCI2010-07614). HK was supported by GABI-FUTURE grant BeetSeq (0315069A) by the German Federal Ministry of Education and Research

Differences in the thoracic aorta by region and sex in a murine model of Marfan Syndrome

Marfan syndrome (MFS) is a hereditary disorder of the connective tissue that causes life-threatening aortic aneurysm, which initiates at the aortic root and can progress into the ascending portion. However, analysis of ascending aorta reactivity in animal models of MFS has remained elusive. Epidemiologic evidence suggests that although MFS is equally prevalent in men and women, men are at a higher risk of aortic complications than non-pregnant women. Nevertheless, there is no experimental evidence to support this hypothesis. The aim of this study was to explore whether there are regional and sex differences in the thoracic aorta function of mice heterozygous for the fibrillin 1 (Fbn1) allele encoding a missense mutation (Fbn1C1039G/+), the most common class of mutation in MFS. Ascending and descending thoracic aorta reactivity was evaluated by wire myography. Ascending aorta mRNA and protein levels, and elastic fiber integrity were assessed by qRT-PCR, Western blotting, and Verhoeff-Van Gieson histological staining, respectively. MFS differently altered reactivity in the ascending and descending thoracic aorta by either increasing or decreasing phenylephrine contractions, respectively. When mice were separated by sex, contractions to phenylephrine increased progressively from 3 to 6 months of age in MFS ascending aortas of males, whereas contractions in females were unchanged. Endothelium-dependent relaxation was unaltered in the MFS ascending aorta of either sex; an effect related to augmented endothelium-dependent hyperpolarization-type dilations. In MFS males, the non-selective cyclooxygenase (COX) inhibitor indomethacin prevented the MFS-induced enhancement of phenylephrine contractions linked to increased COX-2 expression. In MFS mice of both sexes, the non-selective nitric oxide synthase inhibitor L-NAME revealed negative feedback of nitric oxide on phenylephrine contractions, which was associated with upregulation of eNOS in females. Finally, MFS ascending aortas showed a greater number of elastic fiber breaks than the wild-types, and males exhibited more breaks than females. These results show regional and sex differences in Fbn1C1039G/+ mice thoracic aorta contractility and aortic media injuries. The presence of more pronounced aortic alterations in male mice provides experimental evidence to support that male MFS patients are at increased risk of suffering aortic complications