Contributors: Ming Bai, Rolf Georg Beutel, Klaus-Dieter Klass, Weiwei Zhang, Xingke Yang, Benjamin Wipfler
... A new insect species (†Alienopterus brachyelytrus Bai, Beutel, Klass, Wipfler et Zhang gen. et sp. nov.) of a new order and family is described, based on a single male embedded in Cretaceous Burmese amber (ca. 99Ma). Unusual characters are shortened forewings combined with fully developed, operational hindwings, similar as in Dermaptera, and specialized attachment pads otherwise only found in mantophasmatodeans (heelwalkers). A cladistic analysis suggests a placement as sister to Mantodea, supported by a profemoral brush and other characters. The male genitalia show the same pattern in both groups. Specialized features are the unusual flight apparatus, attachment structures adapted for locomotion on leaves, and a dense profemoral setation suitable for catching small prey. †Alienopterus was apparently able to fly and likely a predator of small arthropods in bushes or trees. An impressive radiation of Mantodea started in similar habitats at least 35Ma later in the early Cenozoic. In contrast, †Alienopterus was an evolutionary dead end in the roach–mantis transition zone.
A multi-scale model of the interplay between cell signalling and hormone transport in specifying the root meristem of Arabidopsis thaliana
Contributors: D. Muraro, A. Larrieu, M. Lucas, J. Chopard, H. Byrne, C. Godin, J. King
... The growth of the root of Arabidopsis thaliana is sustained by the meristem, a region of cell proliferation and differentiation which is located in the root apex and generates cells which move shootwards, expanding rapidly to cause root growth. The balance between cell division and differentiation is maintained via a signalling network, primarily coordinated by the hormones auxin, cytokinin and gibberellin. Since these hormones interact at different levels of spatial organisation, we develop a multi-scale computational model which enables us to study the interplay between these signalling networks and cell-cell communication during the specification of the root meristem. We investigate the responses of our model to hormonal perturbations, validating the results of our simulations against experimental data. Our simulations suggest that one or more additional components are needed to explain the observed expression patterns of a regulator of cytokinin signalling, ARR1, in roots not producing gibberellin. By searching for novel network components, we identify two mutant lines that affect significantly both root length and meristem size, one of which also differentially expresses a central component of the interaction network (SHY2). More generally, our study demonstrates how a multi-scale investigation can provide valuable insight into the spatio-temporal dynamics of signalling networks in biological tissues.
Contributors: Arjen P. Stroeven, Clas Hättestrand, Johan Kleman, Jakob Heyman, Derek Fabel, Ola Fredin, Bradley W. Goodfellow, Jonathan M. Harbor, John D. Jansen, Lars Olsen
... To provide a new reconstruction of the deglaciation of the Fennoscandian Ice Sheet, in the form of calendar-year time-slices, which are particularly useful for ice sheet modelling, we have compiled and synthesized published geomorphological data for eskers, ice-marginal formations, lineations, marginal meltwater channels, striae, ice-dammed lakes, and geochronological data from radiocarbon, varve, optically-stimulated luminescence, and cosmogenic nuclide dating. This is summarized as a deglaciation map of the Fennoscandian Ice Sheet with isochrons marking every 1000 years between 22 and 13 cal kyr BP and every hundred years between 11.6 and final ice decay after 9.7 cal kyr BP.
Research Report - Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation defects in zebrafish
Contributors: Jun Wen, Xunsha Sun, Huimin Chen, Huijiao Liu, Rong Lai, Jiaoxing Li, Yufang Wang, Jingjing Zhang, Wenli Sheng
... Moyamoya disease (MMD) is characterized by a stenosis at the terminal of the internal carotid artery and an abnormal vascular network at the base of the brain. RNF213 is a susceptibility gene for MMD in East Asians. The role of RNF213 in the etiology of MMD remains unknown. Here we generated rnf213a mutant zebrafish using transcription activator-like effector nuclease (TALEN) technique and described the characteristics of a zebrafish embryonic model of MMD. rnf213a mutant zebrafish developed abnormal angiogenesis in intersegmental vessels and cranial secondary vessels. Endothelial cells exhibited the defects in morphogenesis and formation of vascular tubes despite normal cell to cell contacts under electron microscope. Circulatory disorder was induced by abnormal sprouts in the trunk and head. Reduced circulation in the abnormal vessels was revealed by microangiography. No blood flow permeated across the vessels wall despite the extremely abnormal structure. rnf213a mutant showed lower erythrocyte velocity in dorsal aorta than that in wild-type siblings. In this study, we provided a promising in vivo model for MMD, and this model would aid to understand the function of rnf213a in angiogenesis.
Contributors: Genevieve Abbruzzese, Sarah F. Becker, Jubin Kashef, Dominique Alfandari
... The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.
Contributors: Zachary R. Conley, Molly Hague, Hiroshi Kurosaka, Jill Dixon, Michael J. Dixon, Paul A. Trainor
... The palate functions as the roof of the mouth in mammals, separating the oral and nasal cavities. Its complex embryonic development and assembly poses unique susceptibilities to intrinsic and extrinsic disruptions. Such disruptions may cause failure of the developing palatal shelves to fuse along the midline resulting in a cleft. In other cases the palate may fuse at an arch, resulting in a vaulted oral cavity, termed high-arched palate. There are many models available for studying the pathogenesis of cleft palate but a relative paucity for high-arched palate. One condition exhibiting either cleft palate or high-arched palate is Treacher Collins syndrome, a congenital disorder characterized by numerous craniofacial anomalies. We quantitatively analyzed palatal perturbations in the Tcof1+/− mouse model of Treacher Collins syndrome, which phenocopies the condition in humans. We discovered that 46% of Tcof1+/− mutant embryos and new born pups exhibit either soft clefts or full clefts. In addition, 17% of Tcof1+/− mutants were found to exhibit high-arched palate, defined as two sigma above the corresponding wild-type population mean for height and angular based arch measurements. Furthermore, palatal shelf length and shelf width were decreased in all Tcof1+/− mutant embryos and pups compared to controls. Interestingly, these phenotypes were subsequently ameliorated through genetic inhibition of p53. The results of our study therefore provide a simple, reproducible and quantitative method for investigating models of high-arched palate.
Original Contribution - Altered mitochondrial dynamics and response to insulin in cybrid cells harboring a diabetes-susceptible mitochondrial DNA haplogroup
Contributors: Hsiao-Mei Kuo, Shao-Wen Weng, Alice Y.W. Chang, Hung-Tu Huang, Hung-Yu Lin, Jiin-Haur Chuang, Tsu-Kung Lin, Chia-Wei Liou, Ming-Hong Tai, Ching-Yi Lin
... The advantage of using a cytoplasmic hybrid (cybrid) model to study the genetic effects of mitochondria is that the cells have the same nuclear genomic background. We previously demonstrated the independent role of mitochondria in the pathogenesis of insulin resistance (IR) and pro-inflammation in type 2 diabetes. In this study, we compared mitochondrial dynamics and related physiological functions between cybrid cells harboring diabetes-susceptible (B4) and diabetes-protective (D4) mitochondrial haplogroups, especially the responses before and after insulin stimulation. Cybrid B4 showed a more fragmented mitochondrial network, impaired mitochondrial biogenesis and bioenergetics, increased apoptosis and ineffective mitophagy and a low expression of fusion-related molecules. Upon insulin stimulation, increases in network formation, mitochondrial DNA (mtDNA) content, and ATP production were observed only in cybrid D4. Insulin promoted a pro-fusion dynamic status in both cybrids, but the trend was greater in cybrid D4. In cybrid B4, the imbalance of mitochondrial dynamics and impaired biogenesis and bioenergetics, and increased apoptosis were significantly improved in response to antioxidant treatment. We concluded that diabetes-susceptible mtDNA variants are themselves resistant to insulin.
Original Articles - Glioma cell dispersion is driven by α5 integrin-mediated cell–matrix and cell–cell interactions
Contributors: Anne-Florence Blandin, Fanny Noulet, Guillaume Renner, Marie-Cécile Mercier, Laurence Choulier, Romain Vauchelles, Philippe Ronde, Franck Carreiras, Nelly Etienne-Selloum, Gyorgy Vereb
... Glioblastoma multiform (GBM) is the most common and most aggressive primary brain tumor. The fibronectin receptor, α5 integrin is a pertinent novel therapeutic target. Despite numerous data showing that α5 integrin support tumor cell migration and invasion, it has been reported that α5 integrin can also limit cell dispersion by increasing cell–cell interaction. In this study, we showed that α5 integrin was involved in cell–cell interaction and gliomasphere formation. α5-mediated cell–cell cohesion limited cell dispersion from spheroids in fibronectin-poor microenvironment. However, in fibronectin-rich microenvironment, α5 integrin promoted cell dispersion. Ligand-occupied α5 integrin and fibronectin were distributed in fibril-like pattern at cell–cell junction of evading cells, forming cell–cell fibrillar adhesions. Activated focal adhesion kinase was not present in these adhesions but was progressively relocalized with α5 integrin as cell migrates away from the spheroids. α5 integrin function in GBM appears to be more complex than previously suspected. As GBM overexpressed fibronectin, it is most likely that in vivo, α5-mediated dissemination from the tumor mass overrides α5-mediated tumor cell cohesion. In this respect, α5-integrin antagonists may be useful to limit GBM invasion in brain parenchyma.
Signaling through the G-protein-coupled receptor Rickets is important for polarity, detachment, and migration of the border cells in Drosophila
Contributors: Lauren Anllo, Trudi Schüpbach
... Cell migration plays crucial roles during development. An excellent model to study coordinated cell movements is provided by the migration of border cell clusters within a developing Drosophila egg chamber. In a mutagenesis screen, we isolated two alleles of the gene rickets (rk) encoding a G-protein-coupled receptor. The rk alleles result in border cell migration defects in a significant fraction of egg chambers. In rk mutants, border cells are properly specified and express the marker Slbo. Yet, analysis of both fixed as well as live samples revealed that some single border cells lag behind the main border cell cluster during migration, or, in other cases, the entire border cell cluster can remain tethered to the anterior epithelium as it migrates. These defects are observed significantly more often in mosaic border cell clusters, than in full mutant clusters. Reduction of the Rk ligand, Bursicon, in the border cell cluster also resulted in migration defects, strongly suggesting that Rk signaling is utilized for communication within the border cell cluster itself. The mutant border cell clusters show defects in localization of the adhesion protein E-cadherin, and apical polarity proteins during migration. E-cadherin mislocalization occurs in mosaic clusters, but not in full mutant clusters, correlating well with the rk border cell migration phenotype. Our work has identified a receptor with a previously unknown role in border cell migration that appears to regulate detachment and polarity of the border cell cluster coordinating processes within the cells of the cluster themselves.
Contributors: Johannes Kamp, Ronny Hänsch, Gregor Kendzierski, Matthias Kraume, Olaf Hellwich
... The fundamental analysis of drop coalescence probability in liquid/liquid systems is necessary to reliably predict drop size distributions in technical applications. For this crucial investigation two colliding oil drops in continuous water phase were recorded with different high speed camera set-ups under varying conditions. In order to analyze the huge amount of recorded image sequences with varying resolutions and qualities, a robust automated image analysis was developed. This analysis is able to determine the trajectories of two colliding drops as well as the important events of drop detachment from cannulas and their collision. With this information the drop velocity in each sequence is calculated and mean values of multiple drop collisions are determined for serial examinations of single drop collisions. Using the developed automated image analysis for drop trajectory and velocity calculation, approximately 1–2 recorded high speed image sequences can be evaluated per minute.