The mechanical control of nervous system development.

The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.This work was supported by the Medical Research CouncilThis is the accepted version of the original publication available at http://dev.biologists.org/content/140/15/3069

Force Generation by Molecular-Motor-Powered Microtubule Bundles; Implications for Neuronal Polarization and Growth.

The heavily cross-linked microtubule (MT) bundles found in neuronal processes play a central role in the initiation, growth and maturation of axons and dendrites; however, a quantitative understanding of their mechanical function is still lacking. We here developed computer simulations to investigate the dynamics of force generation in 1D bundles of MTs that are cross-linked and powered by molecular motors. The motion of filaments and the forces they exert are investigated as a function of the motor type (unipolar or bipolar), MT density and length, applied load, and motor connectivity. We demonstrate that only unipolar motors (e.g., kinesin-1) can provide the driving force for bundle expansion, while bipolar motors (e.g., kinesin-5) oppose it. The force generation capacity of the bundles is shown to depend sharply on the fraction of unipolar motors due to a percolation transition that must occur in the bundle. Scaling laws between bundle length, force, MT length and motor fraction are presented. In addition, we investigate the dynamics of growth in the presence of a constant influx of MTs. Beyond a short equilibration period, the bundles grow linearly in time. In this growth regime, the bundle extends as one mass forward with most filaments sliding with the growth velocity. The growth velocity is shown to be dictated by the inward flux of MTs, to inversely scale with the load and to be independent of the free velocity of the motors. These findings provide important molecular-level insights into the mechanical function of the MT cytoskeleton in normal axon growth and regeneration after injury.We thank François Nédélec for his help with the Cytosim software and to Sarah Foster and Thomas Martin for proofreading. We are grateful to the UK Medical Research Council (Career Development Award to KF), the Israel Science Foundation (grant no. 1396/09 to AZ) and the Bonn Cologne Graduate School as well as Erasmus+ (MJ) for financial support.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fncel.2015.0044

Vergleich von zwei Rinderrassen hinsichtlich ihrer Eignung zur Ökologischen Milchproduktion – Teilfrage: Tiergesundheit

According to the rules of organic farming, prophylaxis shall be supported by selection of appropriate breeds. Nevertheless, today high yielding breeds predominate in organic dairy herds. Since 2004 the Institute of Organic Farming in Trenthorst compares two breeds under the same management conditions on its experimental farm. The evaluation of the data gained between March 2006 and March 2008 revealed a higher treatment rate in the milk orientated Holstein-Friesian cows compared to the German Red Pied, a local dual purpose breed. Although treatment of claw disorders were much more frequent in Holstein-Friesian cows, the lameness scoring carried out every fortnight did not show any difference between the two breeds (Chi2 3=3.506, n. s.). In 24 of 134 cases, cows needed support during calving but the frequency did not differ between the groups (Chi2 2=0.125, n. s.). Due to the low cell frequency the reasons for culling could not be evaluated, yet. Even if a comparison of breeds has to take into account the genotype-environment-interactions, these first results show no clear advantage of an assumed robust breed under the conditions of our organic farm

Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding

Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV-like RNAs and that Z is a powerful inhibitor of these processes (Lopez et al., J. Virol. 65:12241-12251, 2001). More recently, we provided the first evidence of an interaction between Z and L and showed that Z's inhibitory activity was dependent on its ability to bind to L (Jácamo et al., J. Virol. 77:10383-10393, 2003). In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z.Fil: Wilda, Maximiliano. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Casabona, Juan Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Franze Fernandez, Maria T.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentin

Optische Erscheinungen und andere ungewöhnliche Wetterphänomene auf der Wetterwarte Fichtelberg

Der Fichtelberg im Erzgebirge ist mit 1215 Metern die höchste Erhebung Sachsens und liegt an der Grenze zu Tschechien. Gemeinsam mit dem nahe gelegenen Keilberg (heute tschechisch Klínovec; 1244 m) auf böhmischer Seite bildet er den höchsten Punkt des Erzgebirgskamms. Die von Südwest nach Nordost ansteigende Pultscholle des Gebirges fällt nach Süden hin steil ins Egertal (heute tschechisch Údolí Ohře) ab. In diesem, nach Süden vom Duppauer Gebirge (heute tschechisch Doupovské hory) und dem Kaiserwald (heute tschechisch Slavkovský les) eingerahmten Tal sammelt sich bei herbstlichen und winterlichen Hochdruckwetterlagen die Kaltluft (Böhmischer Nebel). Durch diese Konstellation liegt der Fichtelberg entweder in einer trockenen warmen Luftmasse darüber (Inversion) oder er wird direkt vom Böhmischen Nebel beeinflusst, wenn dieser über den Kamm fließt. Das führt zu zahlreichen optischen Erscheinungen, die es sonst in dieser Fülle nur selten gibt. So besticht der Gipfel bei Inversionswetterlagen nicht nur mit einer außergewöhnlichen Fernsicht,Der Fichtelberg im Erzgebirge ist mit 1215 Metern die höchste Erhebung Sachsens und liegt an der Grenze zu Tschechien. Gemeinsam mit dem nahe gelegenen Keilberg (heute tschechisch Klínovec; 1244 m) auf böhmischer Seite bildet er den höchsten Punkt des Erzgebirgskamms. Die von Südwest nach Nordost ansteigende Pultscholle des Gebirges fällt nach Süden hin steil ins Egertal (heute tschechisch Údolí Ohře) ab. In diesem, nach Süden vom Duppauer Gebirge (heute tschechisch Doupovské hory) und dem Kaiserwald (heute tschechisch Slavkovský les) eingerahmten Tal sammelt sich bei herbstlichen und winterlichen Hochdruckwetterlagen die Kaltluft (Böhmischer Nebel). Durch diese Konstellation liegt der Fichtelberg entweder in einer trockenen warmen Luftmasse darüber (Inversion) oder er wird direkt vom Böhmischen Nebel beeinflusst, wenn dieser über den Kamm fließt. Das führt zu zahlreichen optischen Erscheinungen, die es sonst in dieser Fülle nur selten gibt. So besticht der Gipfel bei Inversionswetterlagen nicht nur mit einer außergewöhnlichen Fernsicht, sondern auch mit ungewöhnlich starken Refraktionseffekten wie Luftspiegelungen, stark deformierter oder geteilter Sonnenscheibe sowie mehrfachen Grünen, Blauen und Roten Strahlen an der horizontnahen Sonne. Die Dämmerungsfarben sind bei derartigen Wetterlagen sehr intensiv und neben Purpur- und Gegenpurpurlicht und stark ausgeprägtem Erdschattenbogen zeichnen sich manchmal auch die Schatten weit entfernter Berge oder Wolken am Himmel ab (Crepuscularstrahlen). Fließt der Böhmische Nebel über den Erzgebirgskamm, entstehen bei gleichzeitigem Sonnenschein im Sommer Glorie und Nebelbogen und im Winter atemberaubende Eisnebelhalos. sondern auch mit ungewöhnlich starken Refraktionseffekten wie Luftspiegelungen, stark deformierter oder geteilter Sonnenscheibe sowie mehrfachen Grünen, Blauen und Roten Strahlen an der horizontnahen Sonne. Die Dämmerungsfarben sind bei derartigen Wetterlagen sehr intensiv und neben Purpur- und Gegenpurpurlicht und stark ausgeprägtem Erdschattenbogen zeichnen sich manchmal auch die Schatten weit entfernter Berge oder Wolken am Himmel ab (Crepuscularstrahlen). Fließt der Böhmische Nebel über den Erzgebirgskamm, entstehen bei gleichzeitigem Sonnenschein im Sommer Glorie und Nebelbogen und im Winter atemberaubende Eisnebelhalos

Assembly of the Auditory Circuitry by a Hox Genetic Network in the Mouse Brainstem

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem

Müller glia provide essential tensile strength to the developing retina.

This is the final version of the article. It first appeared from the Rockefeller University Press via http://dx.doi.org/10.1083/jcb.201503115To investigate the cellular basis of tissue integrity in a vertebrate central nervous system (CNS) tissue, we eliminated Müller glial cells (MG) from the zebrafish retina. For well over a century, glial cells have been ascribed a mechanical role in the support of neural tissues, yet this idea has not been specifically tested in vivo. We report here that retinas devoid of MG rip apart, a defect known as retinoschisis. Using atomic force microscopy, we show that retinas without MG have decreased resistance to tensile stress and are softer than controls. Laser ablation of MG processes showed that these cells are under tension in the tissue. Thus, we propose that MG act like springs that hold the neural retina together, finally confirming an active mechanical role of glial cells in the CNS.This work was funded by a Herchel Smith Postdoctoral Fellowship to R.B.M., the Wellcome Trust programme in Developmental Biology to O.R. and J.O., NIH grants EY14358 (R.O.W.) and EY01730 (Vision Core), MRC Career Development Award and HFSP Young Investigator Grant to K.F., and a Wellcome Trust Investigator Award to W.A.H

Development of the anterior-posterior axis is a self-organising process in the absence of maternal cues in mouse embryo

This work was supported by Wellcome Trust, Grant ID: 098287 (MZG) and EMBO (MB).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/cr.2015.10